INTRODUCTION: Severe acute asthma in children is associated with substantial morbidity and may require pediatric ICU (PICU) admission. The aim of the study was to determine risk factors for PICU admission. METHODS: The study used a retrospective multicenter case-control design. The cases included children admitted to the PICU because of severe acute asthma and a history of out-patient treatment by pediatricians or pediatric pulmonologists. Controls were children with asthma without a PICU admission for severe acute asthma. The children were matched for sex, age, hospital, and time elapsed since the diagnosis of asthma. Fourteen possible risk factors were analyzed. RESULTS: Sixty-six cases were matched to 164 controls. In univariate analysis, all but one of the analyzed variables were significantly associated with PICU-hospitalization. After multivariate conditional logistic regression analysis, 4 risk factors remained significant. These included active or passive smoking, allergies, earlier hospitalization for asthma, and non-sanitized home. CONCLUSIONS: Physicians and parents should be aware of these risk factors, and efforts should be made to counteract them.

Quantitative sensory testing (QST) is often used to measure children’s and adults’ detection- and pain thresholds in a quantitative manner. In children especially the Thermal Sensory Analyzer (TSA-II) is often applied to determine thermal detection and pain thresholds. As comparisons between studies are hampered by the different testing protocols used, we aimed to present a standard protocol and reference values for thermal detection- and pain thresholds in children. Our standard testing protocol includes reaction time dependent and independent tests and takes about 14–18 min to complete. Reference values were obtained from a sample of 69 healthy term born children and adolescents with a median age of 11.2 years (range 8.2 to 17.9 years old). Seventy-one children were recruited and data of 28 males and 41 females was obtained correctly. We studied possible age and sex differences. This study provides Dutch reference values and presents a standard quantitative sensory testing protocol for children with an age from 8 years onwards. This protocol appeared to be feasible, since only two out of 71 participants were not able to correctly complete the protocol due to attention deficits and were therefore excluded. We found some significant age and sex differences: females were statistically significantly more sensitive for both cold and heat pain compared to males, and the youngest children (8–9 years old) were less sensitive to detect a warm stimulus. The youngest children tend to be more sensitive to heat pain in comparison to older participants, although the difference was not statistically significant. We present a feasible thermal quantitative sensory testing protocol for children and reference values that are easy to interpret and may serve as normative values for future studies.

Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder, characterized by endocrine problems and hyperphagia, indicating hypothalamic-pituitary dysfunction. However, few studies have explored the underlying neurobiology of the hypothalamus and its functional connectivity with other brain regions. Thus, the aim of this study was to examine the anatomical differences of the hypothalamus, mammillary bodies, and pituitary gland as well as resting state functional connectivity of the hypothalamus in children with PWS. Twenty-seven children with PWS (13 DEL, 14 mUPD) and 28 typically developing children were included. Manual segmentations by a blinded investigator were performed to determine the volumes of the hypothalamus, mammillary bodies, and pituitary gland. In addition, brain-wide functional connectivity analysis was performed using the obtained masks of the hypothalamus. Children with PWS showed altered resting state functional connectivity between hypothalamus and right and left lateral occipital complex, compared to healthy controls. In addition, children with PWS had on average a 50% smaller pituitary volume, an irregular shape of the pituitary, and a longer pituitary stalk. Pituitary volume did not increase in volume during puberty in PWS. No volumetric differences in the hypothalamus and mammillary bodies were found. In all subjects, the posterior pituitary bright spot was observed. We report altered functional hypothalamic connectivity with lateral occipital complexes in both hemispheres, which are implicated in response to food and reward system, and absence of connectivity might therefore at least partially contribute to the preoccupation with food in PWS.

We present a case study of a 10-year-old child with severe burns that were misinterpreted as inflicted burns. Because of multiple injuries since early life, the family was under suspicion of child abuse and therefore under supervision of the Child Care Board for 2 years before the boy was burned. Because the boy incurred the burns without feeling pain, we conducted a thorough medical examination and laboratory testing, evaluated detection and pain thresholds, and used MRI to study brain morphology and brain activation patterns during pain between this patient and 3 healthy age- and gender-matched controls. We found elevated detection and pain thresholds and lower brain activation during pain in the patient compared with the healthy controls and reference values. The patient received the diagnosis of hereditary sensory and autonomic neuropathy type IV on the basis of clinical findings and the laboratory testing, complemented with the altered pain and detection thresholds and MRI findings. Hereditary sensory and autonomic neuropathy IV is a very rare congenital pain insensitivity syndrome characterized by the absence of pain and temperature sensation combined with oral mutilation due to unawareness, fractures, and anhidrosis caused by abnormalities in the peripheral nerves. Health care workers should be aware of the potential presence of this disease to prevent false accusations of child abuse.

Beta-blockers are often used during pregnancy to treat cardiovascular diseases. The described neonatal side effects of maternal beta-blocker use are hypoglycemia and bradycardia, but the evidence base for these is yet to be evaluated comprehensively. Hence, this systematic review and meta-analysis was performed to evaluate the potential increased risk for hypoglycemia and bradycardia in neonates exposed to beta-blockers in utero or during lactation. A systematic search of English-language human studies was conducted until 21 April 2021. Both observational studies and randomized controlled trials investigating hypoglycemia and/or bradycardia in neonates following beta-blocker exposure during pregnancy and lactation were included. All articles were screened by two authors independently and eligible studies were included. Pair-wise and proportion-based meta-analysis was conducted and the certainty of evidence (CoE) was performed by standard methodologies. Of the 1.043 screened articles, 55 were included in this systematic review. Our meta-analysis showed a probable risk of hypoglycemia (CoE—Moderate) and possible risk of bradycardia (CoE—Low) in neonates upon fetal beta-blocker exposure. Therefore, we suggest the monitoring of glucose levels in exposed neonates until 24 h after birth. Due to the limited clinical implication, monitoring of the heart rate could be considered for 24 h. We call for future studies to substantiate our findings.

Background: Adequate pain management for preterm born neonates suffering from the extremely painful disease necrotizing enterocolitis (NEC) is essential, since neonatal exposure to pain is related to negative short-term and long-term consequences. The aim of this study was to describe the current pain management and its effectiveness in NEC patients. Methods: In this single-center, retrospective study, neonates (gestational age < 32 weeks and/or birth weight < 1500 g) with NEC Bell’s stage II or III were included. Information on pain (based on COMFORTneo and NRS scores) and analgesic therapy was collected and analyzed for the acute disease period. Results: Of 79 patients included, 74 (94%) received intravenous analgesic therapy: most commonly morphine, fentanyl, and acetaminophen. The median COMFORTneo score was 11 (IQR 10–11), however, 49 patients had at least one COMFORTneo score ≥ 14 indicating pain. Nineteen patients had persistent high pain scores ≥ 14 with a median duration of 7.2 h (IQR 2.8–14.0). Conclusions: This study showed that despite analgesic therapy, most NEC patients showed signs of pain, and in some, pain persisted for several hours. It suggests that current analgesic therapy frequently failed to prevent pain and existing pain was often insufficiently treated. This supports the urgent need for individualized pain management guidelines for NEC patients. Impact: This study is unique in reporting on pain management in neonates suffering from necrotizing enterocolitis (NEC) during the full acute disease period. Despite analgesic therapy, the majority of NEC patients experience pain, and in some patients, pain persists for several hours. These findings highlight the need for improvement of neonatal pain management in NEC patients, including better pain monitoring and guidelines for individualized analgesic therapy. Improved pain management guidelines may help to prevent short-term and long-term consequences of neonatal exposure to pain, as well as excessive exposure to opioids.