PURPOSE: Historically, cancer predisposition syndromes (CPSs) were rarely established for children with cancer. This nationwide, population-based study investigated how frequently children with cancer had or were likely to have a CPS. METHODS: Children (0–17 years) in Denmark with newly diagnosed cancer were invited to participate in whole-genome sequencing of germline DNA. Suspicion of CPS was assessed according to Jongmans’/McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) criteria and familial cancer diagnoses were verified using population-based registries. RESULTS: 198 of 235 (84.3%) eligible patients participated, of whom 94/198 (47.5%) carried pathogenic variants (PVs) in a CPS gene or had clinical features indicating CPS. Twenty-nine of 198 (14.6%) patients harbored a CPS, of whom 21/198 (10.6%) harbored a childhood-onset and 9/198 (4.5%) an adult-onset CPS. In addition, 23/198 (11.6%) patients carried a PV associated with biallelic CPS. Seven of the 54 (12.9%) patients carried two or more variants in different CPS genes. Seventy of 198 (35.4%) patients fulfilled the Jongmans’ and/or MIPOGG criteria indicating an underlying CPS, including two of the 9 (22.2%) patients with an adult-onset CPS versus 18 of the 21 (85.7%) patients with a childhood-onset CPS (p = 0.0022), eight of the additional 23 (34.8%) patients with a heterozygous PV associated with biallelic CPS, and 42 patients without PVs. Children with a central nervous system (CNS) tumor had family members with CNS tumors more frequently than patients with other cancers (11/44, p = 0.04), but 42 of 44 (95.5%) cases did not have a PV in a CPS gene. CONCLUSION: These results demonstrate the value of systematically screening pediatric cancer patients for CPSs and indicate that a higher proportion of childhood cancers may be linked to predisposing germline variants than previously supposed.

The risk of not completing basic school increased with decreasing gestational age. The risk was moderate at ≥31 weeks' gestation and increased steeply at <31 weeks' gestation. The increase at <31 weeks' gestation was only partly explained by cerebral palsy.

Aim  To describe the socio economic achievement of individuals born very preterm (VPT) at the age of 27 to 29 years. Method  Demographic and social data were extracted from national registers for all individuals born between 1974 and 1976 in Denmark (n=208 656). Of these, 203 283 individuals were alive in 2006. We compared VPT individuals (gestational age <33wks, n=1422; 51.8% males, n=736) with individuals born at term (>36wks, n=192 223; 51.1% males, n=98 240), of whom 4.08% (n=58) of the VPT and 0.19% (n=373) of the term individuals had a diagnosis of cerebral palsy (CP). Results  Overall results in the two groups were similar, but significant differences appeared. The VPT group had a lower educational level than the term group: 23.9% versus 16.3% had a basic education (corresponding to attendance at basic school for 9y or less; odds ratio [OR] =1.61, 95% confidence interval [CI] 1.42–1.82). Similarly, 31.9% versus 37.6% had a tertiary education (corresponding to different levels of professional education; OR=0.77, CI 0.69–0.86). Net income was 11% lower in the VPT group and 10.8% versus 5.3% were receiving welfare support (OR=2.14, CI 1.81–2.55). In the VPT group 59% versus 52% did not have children (p<0.001) and there were more individuals living alone without children (28.8% vs 21.8%; OR=1.45, CI 1.29–1.63). Interpretation  VPT birth in the 1970s in Denmark is associated with a highly statistically significant educational and social disadvantage persisting into young adulthood. CP increased the relative risk of social disadvantage in VPT individuals. However, the majority of the survivors are well integrated in society.

IntroductionPreterm birth is associated with increased risk of asthma-like symptoms and purchase of prescription asthma medication in childhood. We investigated whether this association persists into adulthood and whether it is affected by accounting for neonatal respiratory morbidity (acute respiratory disease and bronchopulmonary dysplasia).MethodsA national cohort of all infants born in Denmark in the period 1980–2009 was included in this register study. Data on purchase of asthma medication (combination of inhaled β-2 agonists and other drugs for obstructive airway disease) in 2010–2011 were obtained from the Danish National Prescription Registry. Associations between gestational age (GA), neonatal respiratory morbidity and a cross-sectional evaluation of asthma medication purchase were explored by multivariate logistic regressions.ResultsA full dataset was obtained on 1,790,241 individuals, 84.6% of all infants born in the period. Odds-ratios (95% CI) for the association between GA and purchase of asthma medication during infancy were: 3.86 (2.46–6.04) in GA 23–27 weeks, 2.37 (1.84–3.04) in GA 28–31 weeks and 1.59 (1.43–1.77) in GA 32–36 weeks compared to term infants with GA 37–42 weeks. Associations weakened in older age groups and became insignificant in young adults born extremely and very preterm with odds-ratios: 1.41 (0.63–3.19) and 1.15 (0.83–1.60) in GA 23–27 and 28–31 respectively. When adjusting for neonatal respiratory morbidity, the associations weakened but persisted both in childhood and adolescence.ConclusionThere was a strong dose-response association between gestational age and the purchase of prescription asthma medication in infancy and childhood. This association weakened during adolescence and was mostly non-significant in young adulthood. The increased risk of prescription asthma medication purchase in ex-preterm children could only partly be explained by neonatal respiratory morbidity.

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Complete resection is the treatment of choice for most pediatric brain tumors, but early postoperative MRI for detection of residual tumor may be misleading because of MRI signal changes caused by the operation. PET imaging with amino acid tracers in adults increases the diagnostic accuracy for brain tumors, but the literature in pediatric neurooncology is limited. A hybrid PET/MRI system is highly beneficial in children, reducing the number of scanning procedures, and this is to our knowledge the first larger study using PET/MRI in pediatric neurooncology. We evaluated if additional postoperative 18 F-fluoro-ethyl-tyrosine ( 18 F-FET) PET in children and adolescents would improve diagnostic accuracy for the detection of residual tumor as compared with MRI alone and would assist clinical management. Methods: Twenty-two patients (7 male; mean age, 9.5 y; range, 0-19 y) were included prospectively and consecutively in the study and had 27 early postoperative 18 F-FET PET exams performed preferentially in a hybrid PET/MRI system (NCT03402425). Results: Using follow-up (93%) or reoperation (7%) as the reference standard, PET combined with MRI discriminated tumor from treatment effects with a lesion-based sensitivity/ specificity/accuracy (95% confidence intervals) of 0.

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Background Nausea and vomiting are common and distressing side effects for children receiving chemotherapy. Limited evidence is available to guide antiemetic recommendations; therefore, prospective and reliable evaluation of antiemetic efficacy is needed. Smartphone apps can be used to effortlessly and precisely collect patient-reported outcomes in real time. Objective Our objective was to develop a smartphone app to monitor nausea and vomiting episodes in pediatric cancer patients aged 0 to 18 years and to test its usability and adherence to its use. Methods We used a user-centered design process and the evolutionary prototype model to develop and evaluate the app. Multidisciplinary group discussions and several rounds of patient feedback and modification were conducted. We translated the validated Pediatric Nausea Assessment Tool to assess nausea severity in children aged 4 to 18 years. The child’s own term for nausea was interactively incorporated in the nausea severity question, with response options expressed as 4 illustrative faces. Parent-reported outcomes were used for children aged 0 to 3 years. Reminders were sent using push notifications in order to ensure high response rates. Children aged 0 to 18 years who were undergoing chemotherapy were recruited from the Department of Pediatric Oncology at Copenhagen University Hospital Rigshospitalet to evaluate the app. Results The app’s most important function was to record nausea severity in children. After assistance from a researcher, children aged 4 to 18 years were able to report their symptoms in the app, and parents were able to report symptoms for their children aged 0 to 3 years. Children (n=20, aged 2.0-17.5 years) and their parents evaluated the app prospectively during a collective total of 60 chemotherapy cycles. They expressed that the app was user-friendly, intuitive, and that the time spent on data entry was fair. The response rates were on average 92%, 93%, and 80% for the day before, the first day of, and the next 3 days after chemotherapy, respectively. Researchers and clinicians were able to obtain an overview of the patient’s chemotherapy dates and responses through a secure and encrypted web-based administrative portal. Data could be downloaded for further analysis. Conclusions The user-friendly app could be used to facilitate future pediatric antiemetic trials and to refine antiemetic treatment during chemotherapy.