Preterm neonates undergo many painful procedures as part of their standard care in the neonatal intensive care unit. However, pain treatment is inadequate in many of these routine procedures. In the present study, we investigated the impact and mechanism of combined music and touch intervention (CMT) on the pain response in premature infants. Sixty-two preterm neonates (gestational age of 0.05). After 2 weeks, the Premature Infant Pain Profile scores were significantly higher in the control group than experimental group (13.000 ± 0.461 vs 10.500 ± 0.850, respectively; P < 0.05). The cortisol concentration was not significantly different between the control and experimental groups either at the beginning of hospitalization (131.000 ± 18.190 vs 237.200 ± 43.860, respectively; P > 0.05) or 2 weeks later (162.400 ± 23.580 vs 184.600 ± 21.170, respectively; P > 0.05). However, the serum β-endorphin concentration was higher in the experimental group than in the control group both at the beginning of hospitalization (1.640 ± 0.390 vs 1.179 ± 0.090, respectively; P < 0.05) and 2 weeks later (2.290 ± 0.740 vs 1.390 ± 0.410, respectively; P < 0.05). CMT might decrease the pain response of preterm neonates by significantly improving the β-endorphin concentration, but not the blood cortisol concentration. Current Controlled Trials ISRCTN14131492 . Registered on 01 Aug 2016.

Bronchopulmonary dysplasia (BPD) is the leading cause of chronic lung disease in preterm neonates. Extracellular matrix (ECM) abnormalities reshape lung development, contributing to BPD progression. In the present study, we first discovered that the ECM component fibronectin was reduced in the pulmonary tissues of model mice with BPD induced by lipopolysaccharide (LPS) and hyper-oxygen. Meanwhile, interleukin-33 (IL-33) and other inflammatory cytokines were elevated in BPD lung tissues. LPS stimulated the production of IL-33 in alveolar epithelial cells via myeloid differentiation factor 88 (MyD88), protein 38 (p38), and nuclear factor-kappa B (NF-κB) protein 65 (p65). Following the knockout of either IL-33 or its receptor suppression of tumorigenicity 2 (ST2) in mice, BPD disease severity was improved, accompanied by elevated fibronectin. ST2 neutralization antibody also relieved BPD progression and restored the expression of fibronectin. IL-33 induced the formation of neutrophil extracellular traps (NETs), which degraded fibronectin in alveolar epithelial cells. Moreover, DNase-mediated degradation of NETs was protective against BPD. Finally, a fibronectin inhibitor directly decreased fibronectin and caused BPD-like disease in the mouse model. Our findings may shed light on the roles of IL-33-induced NETs and reduced fibronectin in the pathogenesis of BPD.

Introduction: Vitamin D deficiency and inflammation are involved with bronchopulmonary dysplasia (BPD) in preterm neonates; however, the clinical evidence still remains scarce. We hypothesized that vitamin D and inflammatory cytokines may be risk factors for BPD in infants. Methods: Preterm infants born between 28 and 31 weeks' gestation were recruited between January 2016 and 2017. Blood samples were all collected at corresponding time points. Vitamin D was measured using an automatic biochemical analyzer, and inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10) were measured using ELISA. Results: The baseline characteristics for preterm infants without BPD (non-BPD control, n = 20) or with BPD (n = 19) were similar. In the blood samples collected 24-h post birth, vitamin D was significantly reduced in the BPD neonates (non-BPD vs. BPD, 28.96 ± 3.404 vs. 17.99 ± 2.233 nmol/l, p = 0.0134). Inflammatory cytokines TNF-α, IL-1β, and IL-6 were comparable in both groups. The anti-inflammatory cytokine IL-10, however, was significantly decreased in 24-h blood samples from BPD preterm infants (non-BPD vs. BPD, 44.61 ± 10.48 vs. 11.64 ± 2.351 pg/ml, p = 0.0054). In the BPD infants with mild or moderate disease, vitamin D deficiency was quite similar. IL-10 deficiency, however, was more aggravated in the BPD infants with moderate disease. No changes in Vitamin D or cytokines (TNF-α, IL-1β, IL-6, and IL-10) were observed for blood samples collected 2 or 4 weeks after birth. Conclusion: In our pilot study, Vitamin D and IL-10 levels at 24-h of life were risk factors for the development of BPD in very preterm infants.

Background: Retinopathy of pre-maturity (ROP) is a disorder of the retinal blood vessels in pre-term infants with low birth weight. It is a leading cause of blindness in children. During ROP screening, the use of mydriatic drops and eyelid openers causes pain and discomfort. Pain management strategies include medications and behavioral interventions. The objectives of this study was to investigate the effects of Gentle Human Touch on pain in pre-term infants undergoing screening for ROP.Methods: In this randomized controlled trial, 82 infants in the neonatal intensive care unit at Children's Hospital of Nanjing Medical University who met the ROP screening criteria were randomly assigned to experimental and control groups using the random number table. The infants in the experimental group continuously received Gentle Human Touch during screening, while those in the control group were screened according to the routine procedure. All neonates were administered local eye anesthesia before the screening. The degree of pain was assessed using the Pre-mature Infant Pain Profile score. A double-channel near-infrared spectroscopy device was used to monitor regional cerebral oxygen saturation (rScO₂), while oxygen saturation (SaO₂) and heart rate were measured using pulse oximetry. The Pre-mature Infant Pain Profile score was the primary outcome, while heart rate, SaO₂, and rScO₂ were the secondary outcomes.Results: The gestational age, corrected gestational age, birth weight, and Apgar score at examination and the basal heart rate, SaO₂, and rScO₂ showed no significant intergroup differences (P > 0.05 for all). Both groups demonstrated significant decreases in SaO₂ and rScO₂ in response to the examination (P < 0.05 for all). During the examination, the Pre-mature Infant Pain Profile score (14.82 ± 3.22 vs. 9.29 ± 2.89, respectively; P < 0.05) was significantly higher in the control group than in the experimental group, while rScO₂ (57.61 ± 3.51 vs. 54.76 ± 4.54%, respectively; P < 0.05) and SaO₂ (91.89 ± 6.43 vs. 85.68 ± 8.31%; P < 0.05) were significantly higher in the experimental group than in the control group. There was no significant difference in heart rate changes between the two groups before and after the examination (182.60 ± 3.50 vs. 170.80 ± 3.50 time/min; P > 0.05).Conclusions: The findings of this study suggest that Gentle Human Touch can effectively alleviate pain during ROP screening in pre-mature infants.Clinical Trial Registration: ISRCTN10976481, Registered 06 March 2020, Retrospectively registered.

Objective: This study aimed to evaluate the cerebral protection effect of fentanyl infusion in very preterm infants in the first 72 h of mechanical ventilation. Methods: In this double-blind, randomized, controlled trial, mechanically ventilated newborns (<32 weeks’ gestational age) were randomized to fentanyl (continuous infusion of fentanyl) or placebo (continuous infusion of glucose, controls) in the first 72 h of the mechanical ventilation period. The premature infant pain profile (PIPP), cerebral blood flow velocity, neuron-specific enolase (NSE) concentrations in plasma samples, and cerebral function monitoring (CFM) recordings were evaluated. Results: Twenty-seven infants were allocated to the fentanyl group and 26 to the control group. The fentanyl group had significantly lower PIPP scores than did the control group at 12, 24, 48, and 72 h after the start of infusion (all p < .05). No significant changes in hemodynamic parameters were observed during the observation period using transcranial Doppler flow measurements (p > .05). The fentanyl group had lower NSE levels and higher total CFM scores compared with the control group (both p < .05). Conclusion: In very preterm infants on mechanical ventilation, continuous fentanyl infusion might protect the developing brain by relieving pain during the first 72 h of mechanical ventilation.