Aim: To investigate the impact of the level of pain experienced by infants born preterm on neurodevelopmental outcomes during their stay in a neonatal intensive care unit.Method: In this retrospective data analysis we included all surviving infants born preterm with a gestational age between 23 and 32 weeks from 2011 to 2015, who were assessed using the Neonatal Pain, Agitation, and Sedation Scale and examined at 1 year of age using the Bayley Scales of Infant Development. We excluded all infants who had suffered severe neurological morbidities and undergone surgical interventions.Results: A total of 196 infants born preterm were included in the analyses: 105 in the ‘no pain group’ and 91 in the ‘pain group’. Significant differences between the groups were detected for both mental and motor development (p = 0.003, 95% confidence interval [CI] 2.23–10.92; p = 0.025, 95% CI 0.64–9.78). The results remained significant after controlling for other important medical conditions (p = 0.001, 95% CI −19.65 to −5.40; p = 0.010, 95% CI −16.18 to −2.29).Interpretation: Neonatal pain exposure was associated with altered neurodevelopmental outcomes of infants born very preterm at a corrected age of 12 months. This observation highlights the importance of adequate pain management to reduce the risk of poor neurodevelopmental outcomes in these vulnerable patients.

Background: The aim of this study was to design and validate a new checklist and standardized scenario for assessing providers’ performance during Newborn Life Support (NLS). Methods: We invited twelve experts in Neonatology to take part in a three-step Delphi process. They rated the importance of each item of a newly designed assessment tool to evaluate participants’ performance during Newborn Life Support independently on a numeric rating scale from 1 to 5 (1 = lowest; 5 = highest) and were able to give additional comments. All items achieving a mean rating below four after the third round were deleted. For the reliability of the checklist, we calculated interrater reliability. Results: Using a standardized Delphi process, we revised the initial checklist according to the experts’ ratings and comments. The final assessment tool includes 38 items covering all relevant steps during NLS. The mean expert rating of all items was 4.40. Interrater reliability showed substantial agreement between the two raters in the first draft (κ = 0.80) as well as in the final draft of the checklist (κ = 0.73). Conclusion: We designed a feasible assessment tool for evaluating performance during NLS. We proved the checklist to be valid and reasonable using a Delphi validation process and calculating interrater reliability.

Background: In the last four years, COVID-19 has prompted concerns about children's well-being. While children's physical health may not be severely affected, their psychological well-being is a significant concern. Therefore, we developed an interdisciplinary psychoeducational intervention program for children named CARTOON. The study aimed to assess whether CARTOON helps kindergarten children to better adhere to mandatory hygiene measures, while also investigating its potential to reduce children's anxiety.Methods: A randomized controlled trial was conducted from January and June 2021 in two Viennese kindergartens involving 53 children aged 3–6 years. Children were randomized into an intervention (specific psychoeducational program) and a control group (routine hygiene practices). CARTOON comprised five sessions covering key hygiene and COVID-19 awareness aspects, facilitated by trained staff. Primary outcomes included changes in children's emotional state and knowledge about COVID-19 and hygiene measures. Secondary outcomes assessed CARTOON's long-term impact on knowledge retention and emotional well-being.Results: Children in the intervention group showed increased COVID-19 knowledge from baseline to long-term assessment (3.9 ± 2.4 vs. 5.9 ± 2.0, p = .003). Moreover, children in the intervention group demonstrated significantly improved long-term hygiene knowledge compared to baseline (8.2 ± 2.2 vs. 5.9 ± 2.3, p < 0.001). Additionally, anxiety scores significantly decreased in the intervention group post-intervention compared to baseline (2.2 ± 1.7 vs. 5.6 ± 2.5; p = .01). Regression analysis identified higher age, higher maternal education, and lower family mental stress as knowledge acquisition predictors.Conclusions: Our findings demonstrate the efficacy of our psycho-educational program in enhancing both knowledge about COVID-19 and adherence to hygiene measures among preschool children, while also reducing anxiety related to the pandemic.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04724616.

Background: Preterm infants undergo multiple painful procedures, which may negatively affect neurodevelopment. Proper pain management, including opioid use, is essential. This study aimed to determine the impact of opioid administration in very and extremely preterm infants on cognitive, motor, and behavioral outcomes at the corrected age of 3 years. Methods: This retrospective, single-center study included preterm infants born between 23 and 32 weeks of gestation, admitted to the Medical University of Vienna between 2011 and 2017. Follow-up data were collected at 3 years corrected age. Primary outcomes included behavioral outcomes assessed by the Child Behavior Checklist (CBCL) and cognitive and motor outcomes using the Bayley Scales of Infant Development (BSID). Results: A total of 333 preterm infants were included, with 214 in the non-opioid group (no exposure to opioids) and 119 in the opioid-group (exposure to opioids). Significant differences in cognitive and motor scores were observed between the groups (92.5 (85.5–98.5) vs 88 (79–94) and 85 (76–96) vs 76 (67–85), both p = 0.001). Behavioral outcomes were within the normal range in both groups, although higher depressive scores were noted in the opioid group. Conclusions: Cumulative opioid exposure in neonatal care may negatively impact cognitive and motor development but did not significantly affect overall behavioral outcomes. Impact: Our findings suggest that cumulative opioid exposure in the NICU does not significantly influence overall behavioral problems at the age of 3 years. However, it poses a risk for altered cognitive and motor development. This study highlights the distinct effects of opioid exposure on motor development and cognitive outcomes, while offering a nuanced perspective on behavioral outcomes, filling gaps in understanding the long-term neurodevelopmental consequences in preterm infants. The findings emphasize the need for careful management of opioid administration in NICU settings, balancing pain relief with potential long-term neurodevelopmental risks, while also underscoring the role of confounding factors such as IVH in shaping developmental trajectories.

SHOX deficiency is a common genetic cause of short stature of variable degree. SHOX haploinsufficiency causes Leri–Weill dyschondrosteosis (LWD) as well as nonspecific short stature. SHOX haploinsufficiency is known to result from heterozygous loss-of-function variants with pseudo-autosomal dominant inheritance, while biallelic SHOX loss-of-function variants cause the more severe skeletal dysplasia, Langer mesomelic dyschondrosteosis (LMD). Here we report for the first time the pseudo-autosomal recessive inheritance of LWD in two siblings caused by a novel homozygous non-canonical, leaky splice-site variant in intron 3 of SHOX: c.544+5G>C. Transcript analyses in patient-derived fibroblasts showed homozygous patients to produce approximately equal amounts of normally spliced mRNA and mRNA with the abnormal retention of intron 3 and containing a premature stop codon (p.Val183Glyfs*31). The aberrant transcript was shown to undergo nonsense-mediated mRNA decay, and thus resulting in SHOX haploinsufficiency in the homozygous patient. Six healthy relatives who are of normal height are heterozygous for this variant and fibroblasts from a heterozygote for the c.544+5G>C variant produced wild-type transcript amounts comparable to healthy control. The unique situation reported here highlights the fact that the dosage of SHOX determines the clinical phenotype rather than the Mendelian inheritance pattern of SHOX variants. This study extends the molecular and inheritance spectrum of SHOX deficiency disorder and highlights the importance of functional testing of SHOX variants of unknown significance in order to allow appropriate counseling and precision medicine for each family individual.