The DUX-25 after Twenty-Five Years: New Analyses and Reference Data.

Twenty-five years after its inception, we present new analyses and reference data for the DUX-25, a questionnaire on health-related quality of life for children 8-17 years old and their parents as proxy. Data from 774 healthy children and their caregivers were collected through web-based data collection. Participants were recruited via primary and secondary schools in the Netherlands. The DUX-25 showed adequate psychometric qualities. Using exploratory and confirmatory factor analyses, we were able to support the theorized four-factor model. In addition, a model with five factors emerged in which the factor 'Social' was divided into 'Social Close' and 'Social Far'. A comparison of the outcomes of the PedsQL with those of the DUX-25 provides evidence for a high construct validity of the DUX-25. With the new updated reference data, the DUX-25 can still be used in inpatient and outpatient settings to measure health-related quality of life of children with chronic conditions.

Sex differences in children's health status as measured by the Pediatric Quality of Life Inventory (PedsQL)™: cross-sectional findings from a large school-based sample in the Netherlands.

BACKGROUND: Previous research has shown that female adolescents and adults report lower health status than their male peers. Possibly, this discrepancy already develops during childhood. We collected sex-specific data with the Pediatric Quality of Life Inventory (PedsQL) in a large school-based sample. METHODS: The online version of the PedsQL was administered to healthy Dutch children aged 5-7 years (parent proxy-report), 8-12 years (parent proxy-report and child self-report), and 13-17 years (parent proxy-report and child self-report), recruited through regular primary and secondary schools. Sex differences were assessed using t-tests or Mann-Whitney U-tests. Wilcoxon signed-rank tests and intraclass correlation coefficients served to compare parent proxy-reports with child self-reports. Multivariable linear regression analyses were used to assess the associations of sex of the child, age, and parental educational level with PedsQL scores. RESULTS: Eight hundred eighty-two parents and five hundred eighty one children were recruited from 15 different schools in the Netherlands. Parents of 8-to-12-year-olds reported higher scores on School Functioning for girls than for boys (mean difference [MD]: 6.56, p < 0.001). Parents of 13-to-17-year-olds reported lower scores on Physical and Emotional Functioning for girls than for boys (MDs: 2.14 and 5.79, p = 0.014 and p < 0.001, respectively). Girls aged 8-12 years reported lower scores than boys in this age group on Physical Functioning (MD: 3.09, p = 0.005). Girls aged 13-17 years reported lower scores than boys in this age group on Physical Functioning (MD: 3.67, p < 0.001), Emotional Functioning (MD: 8.11, p < 0.001), and the Total Score (MD 3.26, p = 0.004). No sex differences were found in children aged 5-7 years. Agreement between child self-reports and parent proxy-reports was poor to moderate. CONCLUSIONS: Girls generally had lower PedsQL scores than boys, both in parent proxy-reports and in child self-reports. We recommend to apply sex-specific data when assessing health status using the PedsQL.

Congenital lung abnormality quantification by computed tomography: The CLAQ method.

INTRODUCTION: To date, no consensus has been reached on the optimal management of congenital lung abnormalities, and factors predicting postnatal outcome have not been identified. We developed an objective quantitative computed tomography (CT) scoring method, and assessed its value for clinical decision-making. METHODS: Volumetric CT-scans of all patients born with a congenital lung abnormality between January 1999 and 2018 were assessed. Lung disease was quantified using the newly-developed congenital lung abnormality quantification (CLAQ) scoring method. In 20 equidistant axial slices, cells of a square grid were scored according to the abnormality within. The scored CT parameters were used to predict development of symptoms, and SD scores for spirometry and exercise tolerance (Bruce treadmill test) at 8 years of age. RESULTS: CT-scans of 124 patients with a median age of 5 months were scored. Clinical diagnoses included congenital pulmonary airway malformation (49%), bronchopulmonary sequestration (27%), congenital lobar overinflation (22%), and bronchogenic cyst (1%). Forty-four patients (35%) developed symptoms requiring surgery of whom 28 (22%) patients became symptomatic before a CT-scan was scheduled. Lesional hyperdensity was found as an important predictor of symptom development and decreased exercise tolerance. Using receiver operating characteristic analysis, an optimal cut-off value for developing symptoms was found at 18% total disease. CONCLUSION: CT-quantification of congenital lung abnormalities using the CLAQ method is an objective and reproducible system to describe congenital lung abnormalities on chest CT. The risk for developing symptoms may increase when more than a single lung lobe is affected.

Using three-dimensional ultrasound in predicting complex gastroschisis: A longitudinal, prospective, multicenter cohort study.

OBJECTIVE: To determine whether complex gastroschisis (ie, intestinal atresia, perforation, necrosis, or volvulus) can prenatally be distinguished from simple gastroschisis by fetal stomach volume and stomach-bladder distance, using three-dimensional (3D) ultrasound. METHODS: This multicenter prospective cohort study was conducted in the Netherlands between 2010 and 2015. Of seven university medical centers, we included the four centers that performed longitudinal 3D ultrasound measurements at a regular basis. We calculated stomach volumes (n = 223) using Sonography-based Automated Volume Count. The shortest stomach-bladder distance (n = 241) was determined using multiplanar visualization of the volume datasets. We used linear mixed modelling to evaluate the effect of gestational age and type of gastroschisis (simple or complex) on fetal stomach volume and stomach-bladder distance. RESULTS: We included 79 affected fetuses. Sixty-six (84%) had been assessed with 3D ultrasound at least once; 64 of these 66 were liveborn, nine (14%) had complex gastroschisis. With advancing gestational age, stomach volume significantly increased, and stomach-bladder distance decreased (both P < .001). The developmental changes did not differ significantly between fetuses with simple and complex gastroschisis, neither for fetal stomach volume (P = .85), nor for stomach bladder distance (P = .78). CONCLUSION: Fetal stomach volume and stomach-bladder distance, measured during pregnancy using 3D ultrasonography, do not predict complex gastroschisis.

Omphalocele at school age: What do parents report? A call for long-term follow-up of complex omphalocele patients.

OBJECTIVE: Many children with omphalocele experience morbidity in early life, which could affect long-term outcomes. We determined parent-reported outcomes in school-aged children treated for minor or giant omphalocele. STUDY DESIGN: We sent paper questionnaires to the parents of all children treated for omphalocele in 2000-2012. Giant omphalocele was defined as defect diameter ≥ 5 cm with liver protruding. Motor function (MABC-2 Checklist) was compared with Dutch reference data; cognition (PedsPCF), health status (PedsQL), quality of life (DUX-25) and behavior (Strengths and Difficulties Questionnaire; SDQ) were compared with those of controls (two per child) matched for age, gender and maternal education level. Possible predictors of cognition and behavior were evaluated using linear regression analyses. RESULTS: Of 54 eligible participants, 31 (57%) returned the questionnaires. MABC-2 Checklist scores were normal for 21/26 (81%) children. Cognition, health status, quality of life and behavior were similar to scores of matched controls. One quarter (26%) of children with omphalocele scored ≤ - 1 standard deviation on the PedsPCF, compared with 9% of matched controls (p = 0.07). Giant omphalocele and presence of multiple congenital anomalies (MCA) were most prominently associated with lower PedsPCF scores (giant omphalocele: ß -22.11 (95% CI: -43.65 to -0.57); MCA -23.58 (-40.02 to -7.13)), although not significantly after correction for multiple testing. CONCLUSIONS: Parent-reported outcomes of children with omphalocele at school age are reassuring. Children with an isolated, minor omphalocele do not need extensive long-term follow-up of daily functioning. Those with a giant omphalocele or MCA might be at risk for delayed cognitive functioning at school age; we recommend long-term follow-up to offer timely intervention.

The validity of the viscero-abdominal disproportion ratio for type of surgical closure in all fetuses with an omphalocele.

OBJECTIVE: To determine the predictive value of the fetal omphalocele circumference/abdominal circumference (OC/AC) ratio for type of surgical closure and survival and to describe the trajectory of OC/AC ratio throughout gestation. METHODS: This cohort study included all live-born infants prenatally diagnosed with an omphalocele in our tertiary centre (2000-2017) with an intention to treat. The OC/AC ratio and liver position were determined using 2D ultrasound at three periods during gestation (11-16, 17-26, and/or 30-38 weeks). Primary outcome was type of closure; secondary outcome was survival. In the secondary analyses, the predictive value of the OC/AC-ratio trend for type of closure and survival was assessed. RESULTS: Primary closure was performed in 37/63 (59%) infants, and 54/63 (86%) survived. The OC/AC ratio was predictive for type of closure and survival in all periods. Optimal cut-off values for predicting closure decreased throughout gestation from 0.69 (11-16 weeks) to 0.63 (30-38 weeks). Repeated OC/AC-ratio measurements were available in 33 (73%) fetuses. The trend of the OC/AC ratio throughout gestation was not significantly associated with type of closure. All infants without liver herniation underwent primary closure. CONCLUSION: Type of omphalocele surgical closure and survival can be predicted prenatally on the basis of the OC/AC ratio and liver herniation independent of associated anomalies. LEARNING OBJECTIVE: The reader will be able to use the OC/AC ratio throughout gestation in all omphalocele cases for prediction of type of closure and survival and thus patient counselling.

Gastroschisis at school age: what do parents report?

Children with gastroschisis are at high risk of morbidity in early life, which could affect long-term outcomes. We determined parent-reported outcomes in school-aged children born in 2000-2012, using paper questionnaires. Parent-perceived child vulnerability and motor function were compared with the Dutch reference data; parent-rated data on cognition, health status, quality of life, and behavior were compared with those of controls matched for age, gender, and maternal education level. Of 77 eligible participants, 31 (40%) returned the questionnaires. Parent-reported motor function was normal in 23 (74%) children. Total scores on health status, quality of life, and behavior did not differ significantly from those of matched controls. Children with gastroschisis had lower scores on cognition (median (interquartile range); 109 (87-127)) than their matched controls (124 (113-140); p = 0.04). Neonatal intestinal failure and increased parent-perceived vulnerability were associated with lower scores on cognition (ß - 25.66 (95% confidence interval - 49.41, - 1.91); - 2.76 (- 5.27, - 0.25), respectively).Conclusion: Parent-reported outcomes of school-aged children with gastroschisis were mainly reassuring. Clinicians and parents should be aware of the higher risk of cognitive problems, especially in those with neonatal intestinal failure or increased parent-perceived vulnerability. We recommend multidisciplinary follow-up at school age of children with gastroschisis and neonatal intestinal failure. What is Known: • Many infants with gastroschisis experience morbidity in early life. • Data on developmental outcomes and daily functioning in children with gastroschisis beyond the age of 5 years are scarce and conflicting. What is New: • Parents of school-aged children treated for gastroschisis report normal motor function, health status, quality of life, and behavior. • Children with gastroschisis, especially those with intestinal failure, may be at risk for cognitive problems at school age. Parents who reported their child as being more vulnerable also reported more cognitive problems at school age.

Lung function, exercise tolerance, and physical growth of children with congenital lung malformations at 8 years of age.

OBJECTIVE: To improve counseling on congenital lung malformations (CLM) by describing long-term outcomes of children either operated on or managed by observation. STUDY DESIGN: We analyzed lung function (spirometry), exercise tolerance (Bruce treadmill), and physical growth of 8-year-old children with CLM who participated in our longitudinal prospective follow-up program. The data are shown as median standard deviation scores (SDS) with IQR, or estimated marginal means (95% CI) on the basis of general linear models. RESULTS: Twenty-nine (48%) of the 61 children had required surgery at a median age of 108 (IQR: 8-828) days, and 32 (52%) were managed by observation. In the surgery group, all lung function measurements (except for forced vital capacity [FVC]) were significantly below 0 SDS, with median FEV1 -1.07 (IQR: -1.70 to -0.56), FEV1 /FVC -1.49 (-2.62 to -0.33), and FEF25%-75% -1.95 (-2.57 to -0.63) (all P < 0.001). Children in the observation group had normal FEV1 and FVC, whereas FEV1 /FVC (-0.81 (-1.65 to -0.14)) and FEF25%-75% (-1.14 (-1.71 to -0.22)) were significantly below 0 SDS (both P < 0.001). Mean exercise tolerance was significantly below 0 SDS in both groups (observation: -0.85 (95% CI: -1.30 to -0.41); surgery: -1.25 (-1.69 to -0.80)); eight (28%) children in the observation group and ten (40%) in the surgery group scored <-1 SDS. Physical growth was normal in both groups. CONCLUSION: Children with CLM may be at risk for reduced lung function and exercise tolerance, especially those who required surgery. As little pulmonary morbidity was found in children with asymptomatic CLM, this study supports a watchful waiting approach in this group.

Omphalocele: from diagnosis to growth and development at 2 years of age.

OBJECTIVES: To compare the prenatal frame of reference of omphalocele (ie, survival of fetuses) with that after birth (ie, survival of liveborn neonates), and to assess physical growth and neurodevelopment in children with minor or giant omphalocele up to 2 years of age. DESIGN: We included fetuses and neonates diagnosed in 2000-2012. Physical growth (SD scores, SDS) and mental and motor development at 12 and 24 months were analysed using general linear models, and outcomes were compared with reference norms. Giant omphalocele was defined as defect ≥5 cm, with liver protruding. RESULTS: We included 145 fetuses and neonates. Of 126 (87%) who were diagnosed prenatally, 50 (40%) were liveborn and 35 (28%) survived at least 2 years. Nineteen (13%) neonates were diagnosed after birth. Of the 69 liveborn neonates, 52 (75%) survived and 42 children (81% of survivors) were followed longitudinally. At 24 months, mean (95% CI) height and weight SDS were significantly below 0 in both minor (height: -0.57 (-1.05 to -0.09); weight: -0.86 (-1.35 to -0.37)) and giant omphalocele (height: -1.32 (-2.10 to -0.54); weight: -1.58 (-2.37 to -0.79)). Mental development was comparable with reference norms in both groups. Motor function delay was found significantly more often in children with giant omphalocele (82%) than in those with minor omphalocele (21%, P=0.002). CONCLUSIONS: The prenatal and postnatal frames of reference of omphalocele differ considerably; a multidisciplinary approach in parental counselling is recommended. As many children with giant omphalocele had delayed motor development, we recommend close monitoring of these children and early referral to physical therapy.

Prenatal markers and longitudinal follow-up in simple and complex gastroschisis.

OBJECTIVE: We aimed to identify gestational-age corrected prenatal ultrasound markers of complex gastroschisis, and to compare physical growth and neurodevelopment between children with simple and complex gastroschisis. DESIGN: We included prenatally diagnosed gastroschisis patients from 2000 to 2012 who joined our longitudinal follow-up programme. Associations between complex gastroschisis and prenatal ultrasound markers collected at 30 weeks' gestation and prior to delivery were tested using logistic regression. Physical growth (SD scores (SDS)), mental and psychomotor developmental index (MDI, PDI; Bayley Scales of Infant Development) were recorded at 12 and 24 months. Data were analysed using general linear models and compared with population norms. RESULTS: Data of 61 children were analysed (82% of eligible cases). Extra-abdominal bowel dilatation at 30 weeks' gestation was significantly associated with complex gastroschisis (OR (95% CI): 5.00 (1.09 to 22.98)), with a high negative (88%) but low positive (40%) predictive value. The mean (95% CI) height SDS at 12 months (-0.46 (-0.82 to -0.11)), and weight SDS at 12 and 24 months (-0.45 (-0.85 to -0.05), and -0.44 (-0.87 to -0.01), respectively) fell significantly below 0 SDS. MDI and PDI were significantly below 100 at 24 months; 93 (88 to 99) and 83 (78 to 87), respectively). Children with complex gastroschisis had a significantly lower PDI (76 (68 to 84)) than those with simple gastroschisis (94 (90 to 97), p<0.001). CONCLUSIONS: Prenatal ultrasound markers could not reliably distinguish between simple and complex gastroschisis. Children with complex gastroschisis may be at increased risk for delayed psychomotor development; they should be monitored more closely, and offered timely intervention.