Jaap Huisman

The long-term follow-up of patients with a congenital diaphragmatic hernia: a broad spectrum of morbidity

Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly with a mortality rate of approximately 40–50%, depending on case selection. It has been suggested that new therapeutic modalities such as nitric oxide (NO), high frequency oxygenation (HFO) and extracorporal membrane oxygenation (ECMO) might decrease mortality associated with pulmonary hypertension and the sequelae of artificial ventilation. When these new therapies indeed prove to be beneficial, a larger number of children with severe forms of CDH might survive, resulting in an increase of CDH-associated complications and/or consequences. In follow-up studies of infants born with CDH, many complications including pulmonary damage, cardiovascular disease, gastro-intestinal disease, failure to thrive, neurocognitive defects and musculoskeletal abnormalities have been described. Long-term pulmonary morbidity in CDH consists of obstructive and restrictive lung function impairments due to altered lung structure and prolonged ventilatory support. CDH has also been associated with persistent pulmonary vascular abnormalities, resulting in pulmonary hypertension in the neonatal period. Long-term consequences of pulmonary hypertension are unknown. Gastro-esophageal reflux disease (GERD) is also an important contributor to overall morbidity, although the underlying mechanism has not been fully understood yet. In adult CDH survivors incidence of esophagitis is high and even Barrett’s esophagus may ensue. Yet, in many CDH patients a clinical history compatible with GERD seems to be lacking, which may result in missing patients with pathologic reflux disease. Prolonged unrecognized GERD may eventually result in failure to thrive. This has been found in many young CDH patients, which may also be caused by insufficient intake due to oral aversion and increased caloric requirements due to pulmonary morbidity. Neurological outcome is determined by an increased risk of perinatal and neonatal hypoxemia in the first days of life of CDH patients. In patients treated with ECMO, the incidence of neurological deficits is even higher, probably reflecting more severe hypoxemia and the risk of ECMO associated complications. Many studies have addressed the substantial impact of the health problems described above, on the overall well-being of CDH patients, but most of them concentrate on the first years after repair and only a few studies focus on the health-related quality of life in CDH patients. Considering the scattered data indicating substantial morbidity in long-term survivors of CDH, follow-up studies that systematically assess long-term sequelae are mandatory. Based on such studies a more focused approach for routine follow-up programs may be established.

Behaviour and school achievement in patients with early and continuously treated phenylketonuria

Thirty patients with early and continuously treated phenylketonuria (PKU) between 8 and 20 years of age were compared with 30 controls, matched individually for age, sex, and educational level of both parents, on behaviour rating scales for parents and teachers as well as a school achievement scale. PKU patients, as a group, demonstrated more problems in task-oriented behaviour and average academic performance than did matched controls. Interestingly, whereas male PKU patients were rated significantly lower on introversion by their teachers, female patients were rated significantly higher on introversion and lower on extraversion than matched controls. This sex difference was also reflected in the relationship between measures of dietary control and the behaviour clusters, suggesting that male and female patients respond differently to elevated Phe levels or the stress associated with PKU. The teacher rating on average academic performance of the PKU patients was associated with recent level of dietary control, which suggests that it might be improved by more strict adherence to the diet. In addition, academic performance correlated negatively with the behaviour cluster negative task orientation. Further studies are recommended to obtain a more complete evaluation of this relationship and to replicate the current findings on larger samples.

Psychological outcome and quality of life in children born with congenital diaphragmatic hernia

Objective: To assess psychological and social functioning and health related quality of life and its early determinants in children born with congenital diaphragmatic hernia (CDH). Design: Cross-sectional follow-up study. Setting: Outpatient clinic of a tertiary care hospital. Participants: 33 CDH survivors aged 6–16 years. Main exposure: Patients who developed CDH associated respiratory distress within 24 h after birth. Main outcome measure: Psychological and social functioning assessed with the Wechsler Intelligence Scale for Children (WISC-R), Bourdon-Vos test, Beery Developmental Test of Visual Motor Integration, Child Behavior Checklist (CBCL) and Teacher Report Form (TRF), and health related quality of life assessed with the Child Health Questionnaire (CHQ) and Health Utilities Index (HUI). Results: Normal mean (SD) total IQ (100.0 (13.2)) and normal visual-motor integration, but significantly lower results for sustained attention (Bourdon-Vos test, 38.8 (11.2) points) were found. Learning difficulties were reported by 30% of parents. Eight children had scores in the clinical range on the CBCL and/or TRF, indicating clinically significant behavioural problems. Except for the CHQ scale General Health, health status was not different from the reference population. No significant correlations between test results and severity of CDH were found, except for an association of general health and physical functioning with length of hospital stay. Conclusion: CDH patients are at risk for subtle cognitive and behavioural problems, probably not related to CDH severity. Perception of general health is reduced compared to the reference population, indicating that CDH survivors and their parents believe their health is poor and likely to get worse.

Impaired sleep affects quality of life in children during maintenance treatment for acute lymphoblastic leukemia: an exploratory study

BackgroundWith the increase of pediatric cancer survival rates, late effects and quality of life (QoL) have received more attention. Disturbed sleep in pediatric cancer is a common clinical observation, but research on this subject is sparse. In general, sleep problems can lead to significant morbidity and are associated with impaired QoL. Information on sleep is essential to develop interventions to improve QoL.MethodsChildren (2-18 years) with acute lymphoblastic leukemia (ALL) were eligible for this multi-center study. The Childrens Sleep Habits Questionnaire (CSHQ), Child Health Questionnaire (CHQ) and Pediatric Quality of Life Inventory 3.0™ Acute Cancer Version (PedsQL) were used to assess sleep and QoL halfway through maintenance therapy. Sleep and QoL were measured during and after dexamethasone treatment (on-dex and off-dex).ResultsSeventeen children participated (age 6.7 ± 3.3 years, 44% boys). Children with ALL had more sleep problems and a lower QoL compared to the norm. There were no differences on-dex and off-dex. Pain (r = -0.6; p = 0.029) and worry (r = -0.5; p = 0.034) showed a moderate negative association with sleep. Reduced overall QoL was moderately associated with impaired overall sleep (r = -0.6; p = 0.014) and more problems with sleep anxiety (r = -0.8; p = 0.003), sleep onset delay (r = -0.5; p = 0.037), daytime sleepiness (r = -0.5; p = 0.044) and night wakenings (r = -0.6; p = 0.017).ConclusionQoL is impaired in children during cancer treatment. The results of this study suggest that impaired sleep may be a contributing determinant. Consequently, enhanced counseling and treatment of sleep problems might improve QoL. It is important to conduct more extensive studies to confirm these findings and provide more detailed information on the relationship between sleep and QoL, and on factors affecting sleep in pediatric ALL and in children with cancer in general.

An overview of studies on early development, cognition, and psychosocial well-being in children born after in vitro fertilization

Objective: To examine whether sufficient research has been done and definite conclusions can be drawn on the psychological outcome of children born after in vitro fertilization (IVF), a review was performed of studies on early development, cognition, and psychosocial well-being in IVF children. Method: PubMed and PsycINFO databases were searched. All English language studies up to 2006 addressing these topics were included. Results: After 25 years of follow-up studies on the development, school outcome, and psychosocial well-being of IVF children, it seems that mental and psychomotor development during the first year and preschool years and cognitive development at 5 years are not deviant. At 6–12 years of age, no differences were observed in cognitive and school performance compared with naturally conceived children; however, the number of studies in this age group is limited. No studies are available that evaluate cognitive aspects and school performance at secondary school age. Overall, positive parent-child relationships were reported in IVF families. In some studies, IVF mothers report more difficulties with their childs behavior only in the childs first year. With regard to the childrens psychosocial well-being, no differences were found up to the age of 8 years. Although after that age, slight indications for some socioemotional and behavioral problems emerged, a large study on the onset of puberty reported that psychosocial functioning was reassuring. Data for adolescents are still lacking. Conclusion: Psychological functioning of those born after IVF is reassuring. However, follow-up should be continued and studies should focus on specific cognitive abilities, school performance, and emotional functioning in adolescence.

Prefrontal dysfunction in early and continuously treated phenylketonuria

In this study, we tested the hypothesis that patients with early and continuously treated phenylketonuria (PKU) are selectively impaired in cognitive functions dependent on the prefrontal cortex (PFC) over a wide age range. Thirty-six patients with PKU between 8 and 20 years of age and 36 controls matched for age, sex, and educational level of both parents performed computerized versions of tests shown to be sensitive to PFC functions. To assess specificity, we selected within each test measures shown to be specifically impaired by PFC damage as well as measures not specifically impaired by damage to the PFC (control measures). A contrast sensitivity test was administered to obtain additional and independent evidence for the mechanism proposed to underlie the specific PFC deficits. Patients with early and continuously treated PKU demonstrated impairments on 3 of the 4 PFC measures but not on any of the control measures. Furthermore, they were found to be significantly less sensitive to contrast than were the matched controls. Together, these results seem to confirm that specific deficits in PFC functions persist in older patients with early and continuously treated PKU. The results with respect to the biochemical mechanism underlying these deficits were less clear. They do suggest, however, that some of the deficits may be ameliorated by stricter dietary treatment.

Long-term psychosocial consequences of hormone treatment for short stature

Aim: To examine psychosocial functioning of young adults with idiopathic short stature or short stature born small for gestational age after growth hormone (GH) and gonadotropin‐releasing hormone agonist (GnRHa) treatment in early adolescence or no intervention.

Effect of dexamethasone on quality of life in children with acute lymphoblastic leukaemia: a prospective observational study.

BackgroundGlucocorticoids are important in the treatment of childhood acute lymphoblastic leukaemia (ALL). However, cyclic administration of high dose glucocorticoids may cause rapid and substantial changes in quality of life (QoL). The maintenance phase of the Dutch ALL-9 protocol consisted of alternating two weeks on and five weeks off dexamethasone (6 mg/m2/day). The present study was performed to assess the effect of dexamethasone on QoL during treatment for ALL according to this protocol.MethodsIn a multicentre prospective cohort study, QoL was assessed halfway (T1) and at the end of the two-year treatment (T2). A generic (Child Health Questionnaire) and disease specific (PedsQL™ cancer version) QoL questionnaire were used to assess QoL in two periods: on and off dexamethasone, respectively.Results41 children (56% males) were evaluated, mean age at diagnosis was 5.6 years. The CHQ physical and psychosocial summary scores were significantly lower than population norms. At T1 and T2, overall QoL showed no significant change. However, regarding specific domains (pain, cognitive functioning, emotion/behaviour and physical functioning) QoL decreased over time. QoL was significantly more impaired during periods on dexamethasone.ConclusionDexamethasone was associated with decreased QoL. At the end of treatment, reported QoL during dexamethasone deteriorated even more on certain scales (pain, cognitive functioning, emotion/behaviour and physical functioning). Knowledge of the specific aspects of QoL is essential to improve counselling and coping in paediatric oncology. Adverse effects of specific drugs on QoL should be taken into account when designing treatment protocols.

Information processing in patients with early and continuously-treated phenylketonuria

A total of 33 patients with early and continuously-treated phenylketonuria (PKU) between 7 and 16 years of age and 33 matched controls participated in a study examining perceptual, central, and response-related mechanisms of information processing. The specific mechanisms studied were: perceptual filtering, memory search, response selection, response execution, and motor presetting. In addition, groups were compared on mean intelligence level and task oriented behaviour. The performance of the PKU patients practically matched that of the controls on all three tasks, suggesting that PKU patients who are continuously maintained on a well-controlled phenylalanine-restricted diet are not impaired in the elementary mechanisms of information processing. Furthermore, groups did not differ in mean IQ or task-oriented behaviour.

School functioning in 8- to 18-year-old children born after in vitro fertilization

The aim of this study was to examine the school functioning of 8- to 18-year-old children born after in vitro fertilization (IVF). We compared 233 children born after IVF to 233 matched control children born spontaneously from parents with fertility problems on measures of education level, general cognitive ability, school performance (need for extra help, repeating a grade, special education), and rates of learning and developmental disorders. No differences were found between IVF and control children on these measures of school functioning. More than 60% of adolescents at secondary school attended high academic levels (with access to high school or university). We conclude that children and adolescents born after IVF show good academic achievement and general cognitive ability. They do not experience any more educational limitations than the naturally conceived children and adolescents of the control group. The tendency of reassuring school functioning already found in younger IVF children has been shown to continue at secondary school age.