Background: The use of technology to support health and health care has grown rapidly in the last decade across all ages and medical specialties. Newly developed eHealth tools are being implemented in long-term management of growth failure in children, a low prevalence pediatric endocrine disorder. Objective: Our objective was to create a framework that can guide future implementation and research on the use of eHealth tools to support patients with growth disorders who require growth hormone therapy. Methods: A total of 12 pediatric endocrinologists with experience in eHealth, from a wide geographical distribution, participated in a series of online discussions. We summarized the discussions of 3 workshops, conducted during 2020, on the use of eHealth in the management of growth disorders, which were structured to provide insights on existing challenges, opportunities, and solutions for the implementation of eHealth tools across the patient journey, from referral to the end of pediatric therapy. Results: A total of 815 responses were collected from 2 questionnaire-based activities covering referral and diagnosis of growth disorders, and subsequent growth hormone therapy stages of the patient pathway, relating to physicians, nurses, and patients, parents, or caregivers. We mapped the feedback from those discussions into a framework that we developed as a guide to integration of eHealth tools across the patient journey. Responses focused on improved clinical management, such as growth monitoring and automation of referral for early detection of growth disorders, which could trigger rapid evaluation and diagnosis. Patient support included the use of eHealth for enhanced patient and caregiver communication, better access to educational opportunities, and enhanced medical and psychological support during growth hormone therapy management. Given the potential availability of patient data from connected devices, artificial intelligence can be used to predict adherence and personalize patient support. Providing evidence to demonstrate the value and utility of eHealth tools will ensure that these tools are widely accepted, trusted, and used in clinical practice, but implementation issues (eg, adaptation to specific clinical settings) must be addressed. Conclusions: The use of eHealth in growth hormone therapy has major potential to improve the management of growth disorders along the patient journey. Combining objective clinical information and patient adherence data is vital in supporting decision-making and the development of new eHealth tools. Involvement of clinicians and patients in the process of integrating such technologies into clinical practice is essential for implementation and developing evidence that eHealth tools can provide value across the patient pathway.

Background Associations between body mass index (BMI), outcome, and leukemia-related factors in children with acute myeloid leukemia (AML) remain unclear. We investigated associations between pretherapeutic BMI, cytogenetic abnormalities, and outcome in a large multinational cohort of children with AML. Methods We included patients, age 2-17 years, diagnosed with de novo AML from the five Nordic countries (2004-2016), Hong Kong (2007-2016), the Netherlands and Belgium (2010-2016), and Canada and USA (1995-2012). BMI standard deviations score for age and sex was calculated and categorized according to the World Health Organization. Cumulative incidence functions, Kaplan-Meier estimator, Cox regression, and logistic regression were used to investigate associations. Results In total, 867 patients were included. The median age was 10 years (range 2-17 years). At diagnosis, 32 (4%) were underweight, 632 (73%) were healthy weight, 127 (15%) were overweight, and 76 (9%) were obese. There was no difference in relapse risk, treatment-related mortality or overall mortality across BMI groups. The frequency of t(8;21) and inv(16) increased with increasing BMI. For obese patients, the sex, age, and country adjusted odds ratio of having t(8;21) or inv(16) were 1.9 (95% confidence interval (CI) 1.1-3.4) and 2.8 (95% CI 1.3-5.8), respectively, compared to healthy weight patients. Conclusions This study did not confirm previous reports of associations between overweight and increased treatment-related or overall mortality in children. Obesity was associated with a higher frequency of t(8;21) and inv(16). AML cytogenetics appear to differ by BMI status.

Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (<27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.

Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) deficiency due to the homozygous PCK1 variant has recently been associated with childhood-onset hypoglycemia with a recognizable pattern of abnormal urine organic acids. In this study, 21 children and 3 adult patients with genetically confirmed PEPCK-C deficiency were diagnosed during the years 2016 to 2019 and the available biochemical and clinical data were collected. All patients were ethnic Finns. Most patients (22 out of 24) had a previously published homozygous PCK1 variant c.925G>A. Two patients had a novel compound heterozygous PCK1 variant c.925G>A and c.716C>T. The laboratory results showed abnormal urine organic acid profile with increased tricarboxylic acid cycle intermediates and inadequate ketone body production during hypoglycemia. The hypoglycemic episodes manifested predominantly in the morning. Infections, fasting or poor food intake, heavy exercise, alcohol consumption, and breastfeeding were identified as triggering factors. Five patients presented with neonatal hypoglycemia. Hypoglycemic seizures occurred in half of the patients (12 out of 24). The first hypoglycemic episode often occurred at the age of 1-2 years, but it sometimes presented at a later age, and could re-occur during school age or adulthood. This study adds to the laboratory data on PEPCK-C deficiency, confirming the recognizable urine organic acid pattern and identifying deficient ketogenesis as a novel laboratory finding. The phenotype is expanded suggesting that the risk of hypoglycemia may continue into adulthood if predisposing factors are present.

Objective. Recent studies have reported an increasing incidence of acute pancreatitis (AP) in children. The etiology of AP in children is more diverse compared to adults. All patients treated for acute pancreatitis (AP) or acute recurrent pancreatitis (ARP) in Helsinki University Children’s hospital during 1999-2018 were reviewed. Methods. ARP was considered as two or more episodes of AP over a lifetime. Demographics, clinical findings, laboratory test results, genetic assessment, imaging findings, endoscopic and surgical treatment, duration of hospital stay, number of pancreatitis episodes, and outcome were analyzed. Results. Of a total of 34 identified patients [n=22 (64%) AP; n=12 (35%) ARP; n=17 (50%) females] none died. The most frequent etiologies were pancreaticobiliary (26%), drug-induced (21%), hereditary (18%), autoimmune (9%) and idiopathic (21%) pancreatitis. An underlying SPINK1 (n=4) and PRSS1 mutation was found in five (15%) patients. Median age at diagnosis was 9.8 (8.2-11) years. Patients with pancreaticobiliary pancreatitis were younger at presentation [4.3 (2.5-9.8) vs. 10 (8.5-12) years, p=0.025] and underwent ERCP (n=7/9 vs. 8/25, p=0.025), and surgical or endoscopic interventions (n= 8/9 vs. 8/25 p=0.006) more frequently compared to the rest of the cohort. The most common long-term complications affecting 29% of patients were chronic upper abdominal pain and diarrhea, occurring each in three patients (8.8%), respectively. Four patients received pancreatic enzyme substitution, while none developed diabetes. Conclusions. Our study highlights the diverse etiology of pediatric pancreatitis necessitating comprehensive diagnostic work-up and management options with relatively low long-term morbidity.

Objective: To quantify soft tissue facial asymmetry (FA) in children with nonsyndromic and Muenke syndrome-associated unicoronal synostosis (NS-UCS and MS-UCS), hypothesizing that MS-UCS presents with significantly larger FA than NS-UCS. Design: Retrospective cohort study. Patients and Methods: Twenty-one children (mean age: 0.6 years; range: 0.1-1.4 years) were included in the study (NS-UCS = 14; MS-UCS = 7). From presurgical computed tomography scans, facial surfaces were constructed for analysis. A landmark guided atlas was deformed to match each patient's surface, obtaining spatially detailed left-right point correspondence. Facial asymmetry was calculated in each surface point across the face, as the length (mm) of an asymmetry vector, with its Cartesian components providing 3 directions. Mean FA was calculated for the full face, and the forehead, eye, nose, cheek, mouth, and chin regions. Results: For the full face, a significant difference of 2.4 mm (P = .001) was calculated between the 2 groups, predominately in the transverse direction (1.5 mm; P < .001). The forehead and chin regions presented with the largest significant difference, 3.5 mm (P = .002) and 3.2 mm (P < .001), respectively; followed by the eye (2.4 mm; P = .004), cheek (2.2 mm; P = .004), nose (1.7 mm; P = .001), and mouth (1.4 mm; P = .009) regions. The transverse direction presented with the largest significant difference in the forehead, chin, mouth, and nose regions, the sagittal direction in the cheek region, and the vertical direction in the eye region. Conclusions: Muenke syndrome-associated unicoronal synostosis presented with significantly larger FA in all regions compared to NS-UCS. The largest significant differences were found in the forehead and chin regions, predominantly in the transverse direction.

Evidence based medicines alongside with age-appropriate dosage forms are essential in enabling appropriate treatment for any patient group. Pediatric pharmacotherapy, however, is lacking age-appropriate dosage forms and research-based evidence regarding the dosing, efficacy, and safety of medicines. Orally administered drugs require manipulation to enable administration and are often used against the indications approved in the marketing authorization and summary of product characteristics (SmPC). This off-label use puts pediatric patients at risk for medicational errors and adverse drug reactions. The aim of this study was to investigate recent trends in oral dosage forms used in pediatric randomized controlled trials (RCTs), with emphasis on age appropriateness. The results could be utilized in developing evidence-based dosage forms, suitable for all pediatric patients aged 0-17 years, and manufacturable in a small scale in a hospital pharmacy. This study was conducted as a systematic review following the PRISMA Statement. The literature search was carried out from Pubmed and Scopus databases and it covered a five-year period of 2015-2020. References from the databases were entered to the Covidence systematic review platform. After removing duplicates 3333 articles were left for screening. Two independent researchers selected the articles first screening by title and abstract, and then by full text review. A qualitative content analysis was conducted on the included articles. Altogether 77 articles met the inclusion criteria. Dosage forms included were tablets (n=37), liquids (n=21), capsules (n=18) and multiparticulates (n=6). Majority of the dosage forms were conventional (n=49) compared to more advanced novel modified release and fixed-dose combination formulations (n=33). Based on our results, orally administered dosage forms used in the recent pediatric RCTs are still limited by poor acceptability, palatability, and the need to manipulate dosage forms to enable administration. These issues are similar to the ones related to the off-label use of medicine that compromise patient safety. Majority of the dosage forms included in our study were tablets, indicating a positive shift towards more safe and acceptable dosage form. Formulations were also evolving towards dispersible, extended-release and fixed-dose combinations that offer additional benefits for pediatric patients. The low number of children < 2 years old included in study populations and the poor acceptability profile reported by most studies limit our conclusions on an ideal age-appropriate dosage form. Further research is needed on unifying the guidelines used in pediatric drug development.

Tämän tutkimuksen tarkoitus oli arvioida painoindeksin yhteyttä fyysiseen suorituskykyyn, rasitusastmareaktioon ja rasituksen laukaisemiin hengitystieoireisiin (yskään, vinkunaan ja hengenahdistukseen) kouluikäisillä lapsilla. 1120 ulkojuoksukokeen tulokset käytiin retrospektiivisesti läpi. Nämä ulkojuoksukokeet oli suoritettu Iho- ja allergiasairaalassa osana kouluikäisten lasten tavanomaisia astmaselvittelyjä. Keuhkojen toimintaa arvioitiin spirometrialla. Astmalle diagnostisen rasituksen laukaiseman keuhkoputkien supistumisen eli rasitusastmareaktion rajana pidettiin vähintään 15 prosentin laskua uloshengityksen sekuntikapasiteetissa rasituksen jälkeen. Fyysinen suorituskyky arvioitiin laskemalla todellisesta juoksuajasta ja -matkasta 6 minuutissa juostu matka. Hengitystieoireet ja -löydökset kirjattiin kokeen aikana, ja lasten ikään ja sukupuoleen suhteutettu painoindeksi eli ISO-BMI laskettiin kansallisia kasvuviitearvoja käyttäen. Suurempi ISO-BMI ja ylipaino ennustivat heikompaa fyysistä suorituskykyä. Lisäksi suurempi ISO-BMI oli yhteydessä yskään ja hengenahdistukseen rasituskokeen aikana. Sen sijaan ISO-BMI ei liittynyt rasitusastmareaktioon eikä vinkunaan. Tämän tutkimuksen löydösten perusteella kouluikäisillä lapsilla ylipaino voi ennustaa heikompaa fyysistä suorituskykyä ja rasitusperäisten hengitystieoireiden ilmaantumista, mutta ei rasitusastmareaktiota. Mikäli asianmukaisia keuhkojen toimintatutkimuksia ei suoriteta, voidaan astmadiagnoosi asettaa väärin perustein. Tutkimus on toistaiseksi suurin kouluikäisten lasten ylipainon, rasitusastmareaktion ja fyysisen suorituskyvyn yhteyttä tarkasteleva tutkimus, mutta koska tutkimus oli luonteeltaan retrospektiivinen asiakirjatutkimus, tulokset tulisi jatkossa vahvistaa prospektiivisella seurantatutkimuksella.

Background: Pediatric physician-led Web-based chat services offer a novel, low-threshold communication channel between caregivers and physicians. Objective: Our aim was to describe chat conversations between caregivers and physicians in a Web-based chat service to determine the factors that should be considered when planning a similar chat service. We also aimed to evaluate whether caregivers considered the consultations helpful, whether physicians considered they could answer caregivers' questions, and whether further face-to-face medical contact was needed. Methods: In September 2015, a private medical center for children in the greater Helsinki area initiated a Web-based chat service, accessible via any device with an internet connection, open from 9 am to 9 pm local time. Four residents in pediatrics, who had performed at least 60% of their 6-year residency program, served as the physicians responsible for chat consultations with caregivers of children. Between October 2015 and March 2016, 343 consecutive consultations were immediately evaluated by a chat physician. On average, caregivers were followed up by email questionnaire 7-14 days later, which 98 caregivers answered a median of 11 (interquartile range, IQR, 7-20) days later. Results: The age of the children whose caregivers contacted the chat service was a median of 2.1 (IQR 0.83-4.69) years, and 29.8% (102/342) of the children were less than 1 year old. The majority (119/343, 34.7%) of the chat conversations took place from 9 am to noon, and infections were the most common concern in over half of cases (189/343, 55.1%). Chat physicians recommended a face-to-face appointment with a physician for that same day in 13.7% (47/343) of the cases. A face-to-face exam was recommended for that same day more often if the chat concerned infection (36/189, 19.0% cases) compared with other reasons (11/154, 7.1%, cases; P=. 001). Physicians felt capable of answering caregivers' questions in 72.6% (249/343) of the cases, whereas 93% (91/98) of caregivers considered physicians' answers helpful. Whether caregivers had to take their children to see a physician that same day or whether caregivers' main concern was infection was not found to be associated with whether caregivers considered physicians' answers helpful or not. However, physicians felt more capable of answering caregivers' questions when the main concern was infection. Conclusions: Parental consultations via Web-based chat service often take place before noon and focus on infection-related issues as well as on the health and illness of very young children. These factors should be considered when planning or setting up such a service. Based on the high satisfaction with the chat service by both physicians and caregivers, Web-based chat services may be a useful way to help caregivers with concerns about their child's health or illness.

Background Malnutrition is related to an increased rate of complications and prolonged hospital stays. Malnutrition risk screening is recommended for all hospital inpatients, but its applicability as part of routine care is not well known. Methods The prevalence of malnutrition risk, measured by the Screening Tool for Risk of Impaired Nutritional Status and Growth (STRONGkids), and acute malnutrition were studied 1 day per year in all pediatric inpatient and day wards in 2015 and 2016 and in inpatients and outpatients in 2017 at a university hospital. Nurses carried out the STRONGkids screening and measured the weight and height of each child, recording the information in the hospital database, where it was subsequently extracted along with data on the child's diagnoses, procedures, and the length and costs of hospital stay. Results In all, 696/1217 patients (57.2%) were screened. Of inpatients and outpatients, 37/398 (9.3%) and 3/298 (1.0%), respectively, were classified as being at high risk of malnutrition. The corresponding figures for those who were acutely malnourished were 18/260 (6.9%) and 11/264 (4.2%). High risk of malnutrition increased the costs and length of hospital stay (P < .05). Dietetic input was involved during hospital stay in 12/37 (32.4%), 32/173 (18.5%), and 13/188 (6.9%) of inpatients at high, moderate, and low risk, respectively (P < .001). Nutrition risk screening did not detect all patients classified as acutely malnourished. Conclusion Hospitals need to ensure proper application of nutrition screening, develop a protocol for the care of children at nutrition risk, and monitor the use of this protocol.