Complications In Preterm Infants Research Articles

A Cohort Study of Serum 25-Hydroxyvitamin D Levels and Lung Disease in Preterm Infants

Objectives: To analyze the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and lung diseases (wet lung, RDS, BPD, pneumothorax) in preterm infants. Methods: Preterm infants (corrected gestational age <37 weeks) hospitalized in the neonatology department of Yan'an University Hospital from January 2023 to December 2023 were selected as the study subjects, and their clinical data and 25-hydroxyvitamin D [25(OH)D] levels in the first 24 h of life were collected (by the random number table method to avoid selection bias) in a retrospective cohort study with the basis of the Serum 25(OH)D level was used to categorize preterm infants into high vitamin D and low vitamin D groups, and to compare the incidence of lung diseases in preterm infants in the 2 groups. Results: A total of 414 preterm infants were selected, and 237 preterm infants were finally included for analysis. The mean serum 25(OH)D level in preterm infants within 24 hours of birth was 16.97 ng/mL. 140 cases in the low-vitamin D group had a serum 25(OH)D level of (11.88± 2.74) ng/mL. 97 cases in the high-vitamin D group had a serum 25(OH)D level of (24.31± 7.52) ng/mL; the rate of births in the fall in the low-vitamin D group was was significantly higher than that of the high-vitamin D group (P<0.05), the utilization rate of lung surface active substance was higher than that of the high-vitamin D group (P<0.05), and the incidence of RDS and BPD was significantly higher than that of the high-vitamin D group (P<0.05). Univariate logistic regression analysis suggested that season of birth, serum 25(OH)D level, 5 min Apgar score and prenatal hormone use were associated with pulmonary complications in preterm infants (P<0.05). Multifactorial logistic regression analysis showed that higher serum 25(OH)D levels reduced the risk of pulmonary complications in preterm infants, which was statistically significant (B=-0.056, RR= 0.946, 95% CI: 0.910-0.984, P=0.006); higher 5-min Apgar scores had a lower incidence of pulmonary complications in preterm infants, which was statistical significance (B=-0.722, RR= 0.486, 95% CI: 0.281~0.840, P=0.010); prenatal use of hormones will reduce the risk of pulmonary complications in preterm infants (B=-0.763, RR= 0.466, 95% CI: 0.261~0.833, P=0.010). Conclusion: Low vitamin D levels at birth in preterm infants may increase the incidence of RDS and BPD.

Effects of Enteral Olive Oil Supplement on Weight Gain, Length of Hospital Stay, and the Development of Some Complications in Preterm Infants: A Randomized Controlled Trial

Effects of Enteral Olive Oil Supplement on Weight Gain, Length of Hospital Stay, and the Development of Some Complications in Preterm Infants: A Randomized Controlled Trial

The pulmonary neuroepithelial body-vagal sensory nerve axis is altered in a mouse model of bronchopulmonary dysplasia (BPD)

Breathing control problems, like apnea of prematurity, are a common complication in preterm infants with bronchopulmonary dysplasia (BPD), but the underlying factors remain incompletely understood. A subpopulation of pulmonary vagal afferent nerve fibers (Calb1+) innervate CO2 and O2 sensitive clusters of lung neuroendocrine cells (neuroepithelial bodies (NEBs)) located along conducting airways. Calb1+ fibers provide direct sensory input to the brainstem that putatively limit tidal volume. NEBs are hyperplastic in BPD infants and may increase activity of inhibitory Calb1+ vagal fibers. Herein, we sought to determine if the NEB-Calb1 lung-brainstem axis is altered in association with breathing control in BPD. BPD in mice was established by exposure to chronic neonatal (postnatal day (P) 0-14) hyperoxia (Hx; 70% O2; n=20) or normoxia (Nx; n=17). Consistent with human BPD, Hx caused alveolar simplification supported by a reduction in alveolar density and alveoli (p<0.05; separate t-tests) in P22 H&E-stained lung sections (n=5-7/group). Like human infants at risk for BPD, Hx mice adapted to increased dead space (caused by reduction in alveoli) by hyperventilating (p<0.05; generalized linear modeling accounting for fat free mass and heat production, measured by NMR and respirometry; n=10-24/group). This was facilitated by an increase in tidal volume that was significantly reduced at P14 but increased at P17 and P21 (n=19-28) (Tukey’s post-hoc: p<0.05). NEBs and associated innervation (vagal and dorsal root ganglia) were next assessed in subsets of mice. First, IT instillation of WGA-594 lectin into subsets of mice (n=9 mice/18 ganglia per group) and subsequent quantification of 594+ neurons per vagal ganglia revealed fewer neurons (p=0.07; t-test) in Hx mice (110.8 ± 6.9 vs 95.2 ± 4.9). Second, CGRP+ innervation to NEBs is reduced in Hx mice (Quantification of CGRP+ nerve fibers only: 17740.4 +/- 4126 vs 10474.6 +/- 2140 +CGRP pixels; p=0.12 n=5-7/group). Third, there was greater frequency of NEBs per unit airway (p<0.05; 0.306 ± 0.03 vs 0.401 ± 0.03) with a tendency for larger NEBs (p=0.06; 9.14 ± 0.7 vs 11.93 ± 1.3) indicating NEB hyperplasia. Together, these data indicate individual NEB innervation is reduced in BPD but that total NEB innervation may remain unchanged. If this is true for Calb1+ vagal fibers remain untested. To functionally assess Calb1-vagal fibers we activated, with DCZ, the excitatory synthetic Gq-DREAD receptor (DTR) expressed in Calb1cre mice via microinjection of AAV-Cre-Gq-mCherry into the left vagal ganglia. DCZ but not vehicle caused a major increase in peak inspiratory flow during acute hypoxic challenges compared to vehicle treated mice (Pre-DMSO, Post-DMSO, Pre-DCZ = ~1ml/sec vs 4ml/sec post-DCZ; p<0.05, n=4/group). Collection of vagal ganglia confirms DTR expression but spillover of DTR is present. Repeating these studies with diluted AAV-Cre-Gq in control and BPD mice are ongoing. Together, our data verify that hyperoxia induced BPD in mice causes a similar reduction in alveoli and compensation to increased dead space by hyperventilation as observed in human BPD. Additionally, BPD structurally alters the NEB-vagal axis but whether these changes are functionally significant to nCOB is being addressed with ongoing studies. AHA 20CDA35310121, Advancing Healthier Wisconsin Endowment. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Direct breastfeeding frequency of late preterm and term infants in the neonatal intensive care unit and availability of mother's own milk at six months of age. a retrospective cohort study.

Mother's Own Milk (MOM) reduces the risk of complications in premature infants. Breastfeeding rates for late preterm and term infants in the neonatal intensive care unit (NICU) are significantly lower than that of breastfed healthy term newborns at 6 months of age. This was a retrospective cohort study of neonates born at 34 weeks 0 days or later. Infants who were directly breastfed in the NICU and were discharged on breastmilk were included. Logistic regression modeling was used to determine the significance of association. 171 mother-infant dyads were included. After adjusting for confounders, the number of breastfeeding attempts during the NICU stay was significantly associated with the availability of MOM at six months of age (p = 0.003, 95% CI 1.02 to 1.14). This study is the first to show an association between the number of direct breastfeeding attempts in the NICU and availability of MOM at six months of age.

Critical period of oxygen supplementation and invasive ventilation: implications for severe retinopathy of prematurity

BackgroundSeveral studies have identified graded oxygen saturation targets to prevent retinopathy of prematurity (ROP), a serious complication in preterm infants. We aimed to analyze the critical period of oxygen supplementation and/or invasive ventilation associated with severe ROP.MethodsThis retrospective case-control study included neonates with a gestational age (GA) < 29 weeks. Participants were divided into two groups: treated retinopathy and untreated/no retinopathy. Time-weighted average FiO2 (TWAFiO2) and weekly invasive ventilation were compared between groups by postnatal age (PNA) and postmenstrual age (PMA). The association of treated retinopathy with TWAFiO2 and invasive ventilation was analyzed.ResultsData from 287 neonates were analyzed; 98 were treated for ROP and had lower GAs (25.5 vs. 27.4 weeks, p < 0.01) and lower birthweights (747.6 vs. 1014 g, p < 0.001) than those with untreated/no ROP. TWAFiO2 was higher from PMA 26–34 weeks, except for PMA 31 weeks in treated ROP, and higher in the first nine weeks of life in treated ROP. On multiple logistic regression, TWAFiO2 and invasive ventilation were associated with ROP treatment during the first seven weeks PNA. Invasive ventilation was associated with ROP treatment from PMA 26–31 weeks; no association was found for TWAFiO2 and PMA.ConclusionsAmount of oxygen supplementation and/or invasive ventilation during the first 7 weeks of life or up to 31 weeks PMA was associated with development of severe ROP. This period might be candidate timing for strict oxygen supplementation strategies in preterm infants, while concerns of mortality with low oxygen supplementation should be further explored.

Quantitative Proteomic Analysis Identifying and Evaluating TRAF6 and IL-8 as Potential Diagnostic Biomarkers in Neonatal Patients with Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a common gastrointestinal complication in premature infants, resulting in high morbidity and mortality, and its early detection is crucial for accurate treatment and outcome prediction. Extensive research has demonstrated a clear correlation between NEC and extremely low birth weight, degree of preterm, formula feeding, infection, hypoxic/ischemic damage, and intestinal dysbiosis. The development of noninvasive biomarkers of NEC from stool, urine, and serum has attracted a great deal of interest because to these clinical connections and the quest for a deeper knowledge of disease pathophysiology. Therefore, this study aims to identify protein expression patterns in NEC and discover innovative diagnostic biomarkers. In this study, we recruited five patients diagnosed with NEC and paired necrotic segments of intestinal tissue with adjacent normal segments of intestine to form experimental and control groups. Quantitative proteomics tandem mass tagging (TMT) labeling technique was used to detect and quantify the proteins, and the expression levels of the candidate biomarkers in the intestinal tissues were further determined by quantitative polymerase chain reaction (RT-qPCR), Western blot analysis, Immunofluorescence methods and enzyme-linked immunosorbent assay (ELISA). A total of 6880 proteins were identified and quantified in patients with NEC. A significant disparity in protein expression was observed between necrotic and normal segments of intestinal tissue in NEC patients. A total of 55 proteins were found to be upregulated, and 40 proteins were found to be downregulated in NEC patients when using a p-value of < 0.05, and an absolute fold change of > 1.2 for analysis. GO function enrichment analysis showed the positive regulation of significant biological processes such as mitochondrial organization, vasoconstriction, rRNA catabolism, fluid shear stress response, and glycerol ether biosynthesis processes. Enrichment analysis also revealed essential functions such as ligand-gated ion channel activity, potassium channel activity, ligand-gated cation channel activity, ligand-gated ion channel activity, and ligand-gated channel activity, including molecular functions such as ligand-gated ion channel activity and mitotic events in this comparative group. Significant changes were found in endomembrane protein complex, membrane fraction, mitochondrial membrane fraction, membrane components, membrane intrinsic components, and other localized proteins. Additional validation of intestinal tissue and serum revealed a substantial increase in TRAF6 (tumor necrosis factor receptor-associated factor 6) and IL-8(Interleukin-8, CXCL8). The quantitative proteomic TMT method can effectively detect proteins with differential expression in the intestinal tissues of NEC patients. Proteins TRAF6 and CXCL8/IL-8 are significantly upregulated in the intestinal tissues and serum samples of patients and may serve as valuable predictor factors for NEC's early diagnosis.

Effects of bradycardia, hypoxemia and early intubation on bronchopulmonary dysplasia in very preterm infants: An observational study

BackgroundBronchopulmonary dysplasia (BPD) is the most common pulmonary complication in preterm infants. ObjectivesThe study aimed to explore the effects of bradycardia, hypoxemia, and early intubation on BPD in very preterm infants. MethodsThis is a prospective observational cohort study. Preterm infants with a mean gestational age of 28.67 weeks were recruited from two level III neonatal intensive care units (NICUs) in Taiwan. Continuous electrocardiography was used to monitor heart rates and oxygen saturation (SpO2). Infants were monitored for heart rates of <100 beats per minute and SpO2 levels of <90 % lasting for 30 s. Generalized estimating equations were used to analyze the effects of bradycardia, hypoxemia, and early intubation on BPD in very preterm infants. Model fit was visually assessed using receiver operating characteristic curve analysis. ResultsBradycardia, hypoxemia, and early intubation significantly increased the odds of BPD among the preterm infants (N = 39) during NICU stay; the odds ratios for bradycardia, hypoxemia, and early intubation for BPD versus non-BPD were 1.058, 1.013, and 29.631, respectively (all p < 0.05). A model combining bradycardia, hypoxemia, and early intubation accurately predicted BPD development (area under the curve = 0.919). ConclusionsBradycardia, hypoxemia, and early intubation significantly increased the odds of BPD among very preterm infants during NICU stay. The model combining bradycardia, hypoxemia, and early intubation accurately predicted BPD development.

Risk factors for postoperative complications in preterm infants with surgical necrotizing enterocolitis and associated outcomes.

We aim to determine clinical risk factors for postoperative complications in preterm infants with surgical necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP). A retrospective cohort study of preterm infants with surgical NEC or SIP to compare clinical factors between those with and without postoperative complications. 78/109 (71.5%) infants had any complication following surgical NEC. Adhesions (20/35, 57.1%) and wound infection (6/35, 17.1%) were the most common single surgical complications. Patients with a single surgical complication (35/66, 53%) were significantly less likely to be exposed to antenatal steroids, more frequently had a jejunostomy, needed a central line longer, and had a longer length of stay than those without any surgical complication. Infants with > 1 surgical complication (43/71, 60.5%) included mainly females, and had AKI more frequently at NEC onset, lower weight z-scores and lower weight for length z- scores at 36 weeks PMA than those without any complications.On multinomial logistic regression, antenatal steroids exposure (OR 0.23 [CI 0.06, 0.84]; p = 0.027) was independently associated with lower risk and jejunostomy 4.81 (1.29, 17.9) was independently associated with higher risk of developing a single complication. AKI following disease onset (OR 5.33 (1.38, 20.6), P = 0.015) was independently associated with > 1 complication in surgical NEC/SIP infants. Infants with postoperative complications following surgical NEC were more likely to be female, have additional morbidities, and demonstrate growth failure at 36 weeks PMA than those without surgical complications. There was no difference in mortality between those with and without surgical complications.

Vasoactive peptides as biomarkers for the prediction of retinopathy of prematurity

BackgroundRetinopathy of prematurity (ROP) is a major complication in preterm infants. We assessed if plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET1) serve as early markers for subsequent ROP development in preterm infants <32 weeks gestation.MethodsProspective, two-centre, observational cohort study. MR-proANP and CT-proET1 were measured on day seven of life. Associations with ROP ≥ stage II were investigated by univariable and multivariable logistic regression models.ResultsWe included 224 infants born at median (IQR) 29.6 (27.1–30.8) weeks gestation and birth weight of 1160 (860–1435) g. Nineteen patients developed ROP ≥ stage II. MR-proANP and CT-proET1 levels were higher in these infants (median (IQR) 864 (659–1564) pmol/L and 348 (300–382) pmol/L, respectively) compared to infants without ROP (median (IQR) 299 (210–502) pmol/L and 196 (156–268) pmol/L, respectively; both P < 0.001). MR-proANP and CT-proET1 levels were significantly associated with ROP ≥ stage II in univariable logistic regression models and after adjusting for co-factors, including gestational age and birth weight z-score.ConclusionsMR-proANP and CT-proET1 measured on day seven of life are strongly associated with ROP ≥ stage II in very preterm infants and might improve early prediction of ROP in the future.ImpactPlasma levels of midregional pro-atrial natriuretic peptide and C-terminal pro-endothelin-1 measured on day seven of life in very preterm infants show a strong association with development of retinopathy of prematurity ≥ stage II.Both biomarkers have the potential to improve early prediction of retinopathy of prematurity.Vasoactive peptides might allow to reduce the proportion of screened infants substantially.

Combined gestational age and serum fucose for early prediction of risk for bronchopulmonary dysplasia in premature infants

ObjectiveAs the predominant complication in preterm infants, Bronchopulmonary Dysplasia (BPD) necessitates accurate identification of infants at risk and expedited therapeutic interventions for an improved prognosis. This study evaluates the potential of Monosaccharide Composite (MC) enriched with environmental information from circulating glycans as a diagnostic biomarker for early-onset BPD, and, concurrently, appraises BPD risk in premature neonates.Materials and methodsThe study incorporated 234 neonates of ≤32 weeks gestational age. Clinical data and serum samples, collected one week post-birth, were meticulously assessed. The quantification of serum-free monosaccharides and their degraded counterparts was accomplished via High-performance Liquid Chromatography (HPLC). Logistic regression analysis facilitated the construction of models for early BPD diagnosis. The diagnostic potential of various monosaccharides for BPD was determined using Receiver Operating Characteristic (ROC) curves, integrating clinical data for enhanced diagnostic precision, and evaluated by the Area Under the Curve (AUC).ResultsAmong the 234 neonates deemed eligible, BPD development was noted in 68 (29.06%), with 70.59% mild (48/68) and 29.41% moderate-severe (20/68) cases. Multivariate analysis delineated several significant risk factors for BPD, including gestational age, birth weight, duration of both invasive mechanical and non-invasive ventilation, Patent Ductus Arteriosus (PDA), pregnancy-induced hypertension, and concentrations of two free monosaccharides (Glc-F and Man-F) and five degraded monosaccharides (Fuc-D, GalN-D, Glc-D, and Man-D). Notably, the concentrations of Glc-D and Fuc-D in the moderate-to-severe BPD group were significantly diminished relative to the mild BPD group. A potent predictive capability for BPD development was exhibited by the conjunction of gestational age and Fuc-D, with an AUC of 0.96.ConclusionA predictive model harnessing the power of gestational age and Fuc-D demonstrates promising efficacy in foretelling BPD development with high sensitivity (95.0%) and specificity (94.81%), potentially enabling timely intervention and improved neonatal outcomes.

Quality improvement in the golden hour for premature infants: a scoping review

Background and objectiveEvidence-based research has shown that golden hour quality improvement (QI) measures can improve the quality of care and reduce serious complications of premature infants. Herein, we sought to review golden hour QI studies to evaluate the impact on the outcome of preterm infants.MethodsA comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, and SinoMed databases from inception to April 03, 2023. Only studies describing QI interventions in the golden hour of preterm infants were included. Outcomes were summarized and qualitative synthesis was performed.ResultsTen studies were eligible for inclusion. All studies were from single centers, of which nine were conducted in the USA and one in Israel. Seven were pre-post comparative studies and three were observational studies. Most included studies were of medium quality (80%). The most common primary outcome was admission temperatures and glucose. Five studies (n = 2308) reported improvements in the admission temperature and three studies (n = 2052) reported improvements in hypoglycemia after QI. Four studies (n = 907) showed that the incidence of bronchopulmonary dysplasia (BPD) was lower in preterm infants after QI: 106/408 (26.0%) vs. 122/424(29.5%) [OR = 0.68, 95% CI 0.48–0.97, p = 0.04].ConclusionsOur study showed that the golden hour QI bundle can improve the short-term and long-term outcomes for extremely preterm infants. There was considerable heterogeneity and deficiencies in the included studies, and the variation in impact on outcomes suggests the need to use standardized and validated measures. Future studies are needed to develop locally appropriate, high-quality, and replicable QI projects.

Early metabolic markers as predictors of respiratory complications in preterm infants with bronchopulmonary dysplasia

BackgroundBronchopulmonary dysplasia (BPD), a common complication of premature birth, exerts considerable impact on the respiratory health of infants. This study aimed to identify the role of plasma metabolites in predicting respiratory outcomes in BPD-afflicted infants. MethodsThis was a case-control study including 15 BPD premature infants and 15 gestational age and birth weight matched no-BPD preterm infants. Plasma samples, obtained at 36 weeks postmenstrual age (PMA), were subjected to a comprehensive analysis of over 300 metabolites using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The respiratory outcomes of the infants were collected with the first 2 years of corrected postnatal age. ResultsThe analysis revealed a significant upregulation of urea and downregulation of nine metabolites in BPD infants, including oxalacetic acid, cis-aconitic acid, itaconic acid, betaine, L-asparagine, L-alanine, picolinic acid, inositol, and purine (p < 0.05). These metabolites primarily pertained to the citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolism, and alanine, aspartate, and glutamate metabolism. Furthermore, seven metabolites demonstrated substantial predictive capacity for respiratory readmissions within the first two years of corrected postnatal age, achieving an area under curve (AUC) exceeding or equal to 0.8. These included chenodeoxycholic acid, dehydrolithocholic acid, glucaric acid, D-glucuronic acid, gamma-glutamylvaline, mevalonic acid, and 3-ureidopropionic acid. ConclusionsThis study identified ten distinct plasma metabolites at 36 weeks PMA that differentiate BPD infants from their non-BPD counterparts, implicating three major metabolic pathways. Additionally, seven metabolites showed strong predictive value for heightened risk of respiratory readmission within two years, underscoring their potential utility in clinical prognostication and management strategies for BPD.

Cerebellar injury in preterm infants less than 28 weeks gestational age.

Cerebellar injury is one of the perinatal complications in preterm infants. Recent studies have highlighted the effect of perinatal complications on neurological morbidity. We investigated the perinatal risk factors and morbidity for cerebellar injury in extremely premature infants. This retrospective cohort study included 285 infants born between April 2009 and December 2020 at gestational age <28 weeks at our institution. The infants were divided into two groups based on magnetic resonance imaging findings: those with and without cerebellar injury. We performed a statistical analysis of the perinatal background and short-term morbidity of the two groups. Significant differences (p < 0.05) were observed between the groups with respect to the perinatal background, especially gestational weeks, birthweight, and hemoglobin values at birth. In the short-term morbidity, significant differences (p < 0.05) were observed in the incidence of respiratory distress syndrome, chronic lung disease, hydrocephalus, severe intraventricular hemorrhage (IVH), and cerebellar hemorrhage. Extensive cerebellar lesions, such as cerebellar agenesis or global cerebellar hypoplasia, accounted for 11 of the 22 cases of cerebellar injury; seven of the 11 cases had severe IVH in addition to cerebellar hemorrhage. Gestational age was significantly lower in the cerebellar injury group. The combination of severe IVH and cerebellar hemorrhage may promote cerebellar injury.

Central line-associated bloodstream infection related with umbilical vein catheterization and peripherally inserted central catheter in preterm infants: a meta-analysis and systematic review

BACKGROUND Central line-associated bloodstream infection (CLABSI) is a serious complication in preterm infants undergoing catheterization, including umbilical vein catheterization (UVC) and peripherally inserted central catheter (PICC) placement. This study aimed to compare the occurrence rate of CLABSI in preterm infants associated with UVC and PICC.&#x0D; METHODS We conducted a systematic review and meta-analysis of studies published from 2000 to 2023 using a random effects model from 3 databases (PubMed, ScienceDirect, and Google Scholar). This study was registered with PROSPERO (CRD42023416471).&#x0D; RESULTS Of 10 articles included in the systematic review, 2 were randomized controlled trials, 3 were prospective studies, and the rest were retrospective. A total of 3,962 UVCs and 2,922 PICCs were incorporated in the meta-analysis. The incidence rate of CLABSI in the UVC group was lower than that in the PICC group (1.23 versus 3.03 per 1,000 catheter days). However, the odds of developing CLABSI for infants with a UVC compared to those with a PICC were not statistically significant (odds ratio: 0.88, 95% confidence interval: 0.54–1.42).&#x0D; CONCLUSIONS UVCs had a lower incidence rate of CLABSI than PICCs. Therefore, additional prospective studies are required to confirm these results.

Predictive and Diagnostic Values of Systemic Inflammatory Indices in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common respiratory complication in preterm infants, and there is a lag in the diagnosis of BPD. Inflammation is a vital pathogenic factor for BPD; we aim to evaluate the predictive and diagnostic values of systemic inflammatory indices in BPD. Between 1 January 2019 and 31 May 2023, the clinical data of 122 premature infants with a gestational age of <32 weeks in the Department of Neonatology, the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, were retrospectively collected and classified into non-BPD (n = 72) and BPD (n = 50) groups based on the National Institute of Child Health and Human Development 2018 criteria. To compare the general characteristics of each group, we identified the independent risk variables for BPD using multivariate logistic regression analysis, compared the systemic inflammatory indices at birth, 72 h, 1 week, 2 weeks, and 36 weeks postmenstrual age (PMA), and constructed the receiver operating characteristic curves of neutrophil-to-lymphocyte ratio (NLR) diagnosis of BPD at different time points. ① The independent risk factors for BPD in preterm infants were birth weight, small for gestational age, and days of oxygen therapy (all p < 0.05). ② At 72 h and 1 week after birth, the serum NLR of the BPD group was higher than for the non-BPD group (p < 0.05). Furthermore, the neutrophil count (N), NLR, monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index, systemic inflammation response index (SIRI), and pan-immune-inflammation value of infants with BPD were higher than the non-BPD group at 3 weeks after birth (p < 0.05). Moreover, at 36 weeks of PMA, the serum N, NLR, MLR, and SIRI of BPD infants were higher than those of non-BPD infants (p < 0.05). ③ The NLR of infants with and without BPD gradually increased after birth, reaching a peak at 72 h and 1 week, respectively. At 3 weeks postnatal, the NLR had the highest predictive power for BPD, with an area under the curve (AUC) of 0.717 (p < 0.001); the sensitivity was 56% and specificity was 86.1%. In addition, the NLR at 36 weeks of PMA exhibited some diagnostic value for BPD. The AUC was 0.693 (p < 0.001), the sensitivity was 54%, and specificity was 83.3%. At 3 weeks after birth and 36 weeks of PMA, some systemic inflammation indices (like N, NLR, SIRI) of preterm infants with BPD have specific predictive and diagnostic values; these indices may help the management of high-risk preterm infants with BPD.

Mesenchymal stromal/stem cells and bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants, leading to chronic respiratory disease. There has been an improvement in perinatal care, but many infants still suffer from impaired branching morphogenesis, alveolarization, and pulmonary capillary formation, causing lung function impairments and BPD. There is an increased risk of respiratory infections, pulmonary hypertension, and neurodevelopmental delays in infants with BPD, all of which can lead to long-term morbidity and mortality. Unfortunately, treatment options for Bronchopulmonary dysplasia are limited. A growing body of evidence indicates that mesenchymal stromal/stem cells (MSCs) can treat various lung diseases in regenerative medicine. MSCs are multipotent cells that can differentiate into multiple cell types, including lung cells, and possess immunomodulatory, anti-inflammatory, antioxidative stress, and regenerative properties. MSCs are regulated by mitochondrial function, as well as oxidant stress responses. Maintaining mitochondrial homeostasis will likely be key for MSCs to stimulate proper lung development and regeneration in Bronchopulmonary dysplasia. In recent years, MSCs have demonstrated promising results in treating and preventing bronchopulmonary dysplasia. Studies have shown that MSC therapy can reduce inflammation, mitochondrial impairment, lung injury, and fibrosis. In light of this, MSCs have emerged as a potential therapeutic option for treating Bronchopulmonary dysplasia. The article explores the role of MSCs in lung development and disease, summarizes MSC therapy's effectiveness in treating Bronchopulmonary dysplasia, and delves into the mechanisms behind this treatment.

Cerebral and intestinal oxygen saturation of different volumes of red blood cell transfusion in preterm infants

ObjectivesThe purpose of this study was to investigate and compare the effects of 20 ml/kg and 15 ml/kg red blood cell transfusion (RBCT) on cerebral and intestinal tissue oxygenation, the number of administered transfusions, and neonatal complications in premature infants with anemia. MethodsThis prospective, randomized, partially blinded observational study investigated anemic neonates of gestational age < 32 weeks (Registration ID: ChiCTR 1,900,026,672). The infants were randomly assigned to receive 15 or 20 ml/kg red blood cell transfusion. Cerebral and intestinal tissue oxygen saturation (cer rSO2 and int rSO2) were collected 2 h before transfusion, 2, 4, 6, 12, 24, and 48 h after the beginning of transfusion by Near-infrared spectroscopy (NIRS). We also collected vital signs including heart rate (HR), peripheral oxygen saturation (SpO2), and mean arterial blood pressure (MABP) 2 h before infusion, 2 h, and 6 h after the beginning of transfusion. Then we analyzed and compared regional oxygen saturation(rSO2), fractional tissue oxygen extraction (FTOE), and other outcome readouts (blood transfusion numbers, changes in hematocrit and hemoglobin, hospitalization days, HR, SpO2, MABP, and complications) between the two groups. The intraindividual comparisons of the above readouts before transfusion and those after transfusion were also evaluated within each group. Result73 newborns received 20 ml/kg (large volume group) and 78 newborns received 15 ml/kg transfusion (small volume group). There was no significant difference in cer rSO2, int rSO2, Cerebral fractional tissue oxygen extraction (cFTOE), and intestinal fractional tissue oxygen extraction (iFTOE) between the two groups. rSO2, MABP, and SpO2 increased; HR, cFTOE, and iFTOE decreased following transfusion in both groups. The transfusion number of the large volume group is significantly less than that of the small volume group (1.9 ± 0.3 vs. 2.6 ± 0.9, p < 0.01) and hospitalization days were also less than those in the low volume group (44.3 ± 8.2 vs. 47.6 ± 9.8, p < 0.05). The increases in hematocrit and hemoglobin were higher in the large volume group than those in small volume (hematocrit increment (%),10.7 ± 4.2 vs. 10.1 ± 5.9, p = 0.015; Hb concentration after blood transfusion (g/L) 132.3 ± 11.1 vs. 127.4 ± 15.4, p = 0.028). ConclusionAfter the transfusion, cer rSO2 and int rSO2 increased significantly, FTOE decreased and vital signs improved in both the 15 ml/kg and 20 ml/kg groups, and these changes were not significantly different between the two groups. However, the larger group showed a more pronounced increase in hematocrit and hemoglobin, a reduction in the total number of transfusions, and a shorter duration of hospitalization after transfusion in preterm infants without increasing complications.

Current diagnosis and treatment practice for pulmonary hypertension in bronchopulmonary dysplasia-A survey study in Germany (PUsH BPD).

Pulmonary hypertension (PH) is the most severe complication in preterm infants with bronchopulmonary dysplasia (BPD) and associated with significant mortality. Diagnostic and treatment strategies, however, still lack standardization. By the use of a survey study (PH in BPD), we assessed clinical practice (diagnosis, treatment, follow-up) in preterm infants with early postnatal persistent pulmonary hypertension of the newborn(PPHN) as well as at risk for or with established BPD-associated PH between 06/2018 and 10/2020 in two-thirds of all German perinatal centers with >70 very low birthweight infants/year including their cardiology departments and outpatient units. Data wereanalyzed descriptively by measures of locations and distributional shares. In routine postnatal care, clinical presentation and echocardiography were reported as the main diagnostic modalities to screen for PPHN in preterm infants, whereas biomarkers brain natriuretic peptide/N-terminal pro b-type natriuretic peptide were infrequently used. For PPHN treatment, inhaled nitric oxidewas used in varying frequency. The majority of participants agreed to prescribe diuretics and steroids (systemic/inhaled) for infants at risk for or with established BPD-associated PH and strongly agreed on recommending respiratory syncytial virus immunization and the use of home monitoring upon discharge. Reported oxygen saturation targets, however, varied in these patients in in- and outpatient care. The survey reveals shared practices in diagnostic and therapeutic strategies for preterms with PPHN and BPD-associated PH in Germany. Future studies are needed to agree on detailed echo parameters and biomarkers to diagnose and monitor disease next to a much-needed agreement on the use of pulmonary vasodilators, steroids, and diuretics as well as target oxygen saturation levels.

The miRNA transcriptome of cerebrospinal fluid in preterm infants reveals the signaling pathways that promote reactive gliosis following cerebral hemorrhage.

Germinal Matrix-Intraventricular Haemorrhage (GM-IVH) is one of the most common neurological complications in preterm infants, which can lead to accumulation of cerebrospinal fluid (CSF) and is a major cause of severe neurodevelopmental impairment in preterm infants. However, the pathophysiological mechanisms triggered by GM-IVH are poorly understood. Analyzing the CSF that accumulates following IVH may allow the molecular signaling and intracellular communication that contributes to pathogenesis to be elucidated. Growing evidence suggests that miRs, due to their key role in gene expression, have a significant utility as new therapeutics and biomarkers. The levels of 2,083 microRNAs (miRs) in 15 CSF samples from 10 infants with IVH were measured using miRNA whole transcriptome sequencing. Gene ontology (GO) and miR family analysis were used to uncover dysregulated signalling which were then validated in vitro in human foetal neural progenitor cells treated with IVH-CSF. Five hundred eighty-seven miRs were differentially expressed in the CSF extracted at least 2 months after injury, compared to CSF extracted within the first month of injury. GO uncovered key pathways targeted by differentially expressed miRs including the MAPK cascade and the JAK/STAT pathway. Astrogliosis is known to occur in preterm infants, and we hypothesized that this could be due to abnormal CSF-miR signaling resulting in dysregulation of the JAK/STAT pathway - a key controller of astrocyte differentiation. We then confirmed that treatment with IVH-CSF promotes astrocyte differentiation from human fetal NPCs and that this effect could be prevented by JAK/STAT inhibition. Taken together, our results provide novel insights into the CSF/NPCs crosstalk following perinatal brain injury and reveal novel targets to improve neurodevelopmental outcomes in preterm infants.

Type 2 innate lymphoid cell-derived amphiregulin regulates type II alveolar epithelial cell transdifferentiation in a mouse model of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants characterized by alveolar growth arrest. Interleukin (IL)-33 and type 2 innate lymphoid cell (ILC2) affect type II alveolar epithelial cell (AECII) differentiation in BPD mice and may cause increased lung epithelial-mesenchymal transition (EMT). Amphiregulin (AREG) can be produced by ILC2 and is associated with tissue repair. However, the action mechanism of AREG produced by ILC2 to alveolar development in BPD is unclear. In this study, we aimed to demonstrate the role and mechanism of AREG in influencing AECII transdifferentiation in the lung tissue of BPD mice. The effects of ILC2-derived AREG on AECII transdifferentiation were verified in vivo and in vitro, and the role of IL-33 on ILC2-derived AREG in AECII transdifferentiation in BPD mice and a preliminary investigation of the role of AREG’s receptor-epidermal growth factor receptor (EGFR) on AECII transdifferentiation. The results showed that neonatal mice developed severe lung injury after hyperoxia, and IL-33 induced AREG production via ILC2 affected normal AECII differentiation and promoted EMT. In addition, the blockade of EGFR was found to alleviate the impaired AECII differentiation under hyperoxia in an in vitro study. In summary, our study demonstrates that AREG secreted by ILC2 affects AECII transdifferentiation in BPD mice, which provides a new idea for the clinical treatment of BPD.