Importance:Existing evidence shows that the environment is a risk factor in preterm birth. However, more evidence is needed about the association between environmental exposures and outcomes of preterm birth. Objective:To examine the association of antepartum exposure to individual and combined indices of greenness, air pollution, and extreme temperatures with outcomes of preterm infants. Design, Setting, and Participants:This cohort study used linked national databases of the Canadian Neonatal Network and Canadian Urban Environmental Health Research Consortium. The cohort consisted of infants born at 22 to 28 weeks plus 6 days' gestation between January 1, 2010, and December 31, 2020, and treated in tertiary neonatal intensive care units (NICUs) across Canada. Data were analyzed between May 1 and September 15, 2024. Exposure:Indices summarizing levels of greenness, air pollutants, and ambient temperature at mothers' residential postal code at birth. Main Outcome and Measure:Infant survival without major morbidity (SWMM) assessed at death or discharge from the NICU. Logistic regression models estimated associations between individual and combination of indices with SWMM. Results:A total of 14 748 infants (7965 males [54.0%]; mean [SD] gestational age, 26.1 [1.6] weeks; median [IQR] birth weight, 890 [720-1090] g) were included. The rate of SWMM was 32.1% (4737 of 14 748). Infants born to mothers who were exposed to high ozone levels had lower odds of SWMM vs infants with mothers exposed to low ozone levels (adjusted odds ratio [AOR], 0.83; 95% CI, 0.74-0.95). Infants with antepartum exposure to low temperature combined with either high levels of ozone (AOR, 0.76; 95% CI, 0.60-0.95) or low levels of greenness (AOR, 0.77; 95% CI, 0.60-0.99) or both low levels of greenness and high levels of ozone (AOR, 0.58; 95% CI, 0.43-0.77) had lower odds of SWMM than infants with mothers who were not exposed to these risk factors. Conclusions and Relevance:In this cohort study, antepartum exposure to high ozone and combined low temperatures and low levels of greenness or high ozone were associated with lower odds of SWMM in preterm infants. These findings suggest that the health outcomes of antepartum environmental exposure extend to neonatal outcomes of preterm infants.

Disrupted immunity and microbiota dysbiosis underlie the pathophysiology of preterm complications. This study investigated the effect of autologous cord blood (ACB)-mononuclear cells (MNCs) infusion, rich in stem cells, on immune microecology in very preterm infants (VPIs). One twin from each enrolled very preterm monozygotic pair was randomized to receive an ACB-MNCs infusion or normal saline. Immune cells, inflammatory cytokine profiles, and gut/lung microbiota, were compared. Short- and long-term clinical outcomes were evaluated. ACB-MNCs intervention induced transcriptional up-regulation of regulatory T cells (Treg) differentiation-facilitating genes and increased circulating Tregs. In blood, post-ACB-MNCs infusion, pro-inflammatory factors decreased, while the IL-10 level was higher than in the control group. In the ACB-MNCs group, lung microbial diversity increased significantly after intervention. Post-intervention, lung IL-10 and TGF-β increased in the ACB-MNCs group and were higher than the control group, while pro-inflammatory factors IL-4, IL-17 A, and IL-6 levels decreased in the ACB-MNCs group. In the ACB-MNCs group, gut microbial diversity improved and was more metabolically active after intervention. After intervention, mainly upregulated differentially expressed genes in peripheral blood immune cells were positively correlated with favored microbes colonizing the lung. Lung IL-10 correlated positively with blood Treg frequency, while lung IL-10 and TGF-β correlated negatively with blood IL-17A. The gut microbial diversity was negatively associated with blood IL-17A. Compared with control group, the total number of distinct preterm complications per patient in the ACB-MNCs group were fewer and long-term linear growth was better. ACB-MNCs intervention promoted immunity homeostasis via modulation of Treg and lung/gut microbiota. This study was registered at Clinicaltrials.gov (NCT05087498). Date of registration: 10/09/2021; date of enrollment of the first participant to the trial:11/28/2021URL of trial registry record: https://clinicaltrials.gov/study/NCT05087498?term=NCT05087498 rank=1 .

The translational potential of human cell therapies for cerebral palsy (CP) is limited by a lack of immune-compatible preclinical models. To address this, we established a CP-like model via intracranial lipopolysaccharide (LPS) injection in neonatal immunodeficient mice. Compared to Sham controls (n = 12), LPS-injected mice (n = 12) exhibited lower survival (83.3% vs. 100%), reduced body weight (23.15 ± 2.07 g vs. 25.53 ± 0.99 g, P < 0.01), and significant motor deficits, including locomotor asymmetry, impaired balance, and hypolocomotion. Gait analysis revealed hindlimb-predominant spatiotemporal abnormalities: prolonged stance, propulsion, and swing durations; reduced stride frequency and stance width; and a divergent forelimb-hindlimb paw angle response. These findings demonstrate that intracranial LPS injection in immunodeficient mice produces a multifaceted CP‑like phenotype featuring hindlimb-predominant gait abnormalities, motor incoordination, and altered exploration. This model could serve as a validated, immune-compatible platform for studying CP pathophysiology and for the preclinical evaluation of human cell therapies.

IntroductionCongenital tuberculosis (CTB) is a rare and life-threatening condition with a mortality rate of approximately 53% even with clinical intervention, which is markedly higher than that of adult tuberculosis (ATB). To date, the phenotypic and functional characteristics of immune cells in CTB neonates remain largely uncharacterized.MethodsIn this case-control study, we enrolled nine CTB neonates and nine paired healthy control (pHC) neonates, collecting basic clinical characteristics of the infants and their mothers, and comparing routine blood test results, C-reactive protein (CRP) levels, and lymphocyte subset profiles via flow cytometry during hospitalization. For exploratory mechanistic investigation, we performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells isolated from one pHC neonate and one CTB neonate at the pre-symptomatic early stage, with additional scRNA-seq data of one ATB patient included for comparative analysis.ResultsAt the clinical level, CTB neonates exhibited gradual lymphocyte depletion, reduced regulatory T (Treg) cell frequency, and an excessive innate immune response-changes that may drive an overwhelming pro-inflammatory response alongside a compromised adaptive immune response. Exploratory scRNA-seq analysis of the single CTB and pHC neonate revealed a general suppression of immune function in T and natural killer (NK) cells in CTB. T cell subset transcriptomic profiling further showed decreased proportions of Tregs, Th1/17 cells, proliferating T cells, and cytotoxic CD8+ T cells in the CTB neonate, with a concomitant reduction in cytotoxic NK cell frequency. The proportion of myeloid cell subsets in CTB was similar to that in HCs, however, myeloid cells in CTB showed a generally activated inflammatory response. Compared with ATB, myeloid cells of CTB expressed high levels of inflammatory markers. Transcriptomic features of T and NK cell function in the CTB neonate were similar to those in the ATB patient, yet these immune cells in the CTB neonate showed a generally weaker antigen presentation capacity. These preliminary features may partially underpin the high mortality of CTB.DiscussionNotably, the scRNA-seq findings presented here are exploratory and hypothesis-generating, and should be interpreted with caution. Further studies with expanded scRNA-seq cohorts are urgently needed to validate these initial observations and elucidate the core immune pathophysiological mechanisms of CTB.

Background We aimed to evaluate the association between initial empirical antibiotic therapy (IEAT) and necrotizing enterocolitis (NEC) in very preterm infants at different early onset sepsis (EOS) risk. Methods This prospective, observational, multi-center study enrolled very low birth weight (VLBW) infants of < 32 weeks' gestation without culture-proven EOS. Infants delivered by cesarean section, without rupture of membranes before delivery, and without maternal chorioamnionitis were categorized as low-risk for EOS. Competing risk Cox regression analysis and cumulative incidence function curves were used to analyse the association between the duration of IEAT (0 days, < 3 days, 3-5 days or > 5 days) and NEC cumulative incidence, and death was considered as a competing risk. Finally, restricted cubic spline (RCS) models were used to further examine the relationship between time-varying antibiotic exposure and the risk of NEC. Results Of the 11678 included infants, 2767 infants were categorized as low risk for EOS. In the whole cohort and the infants with non-low-risk EOS, IEAT < 3 days showed a significantly lower risk of NEC (adjusted sHR 0.36, 95% CI [0.19,0.68]; (adjusted sHR 0.40, 95% CI [0.21, 0.79]) and IEAT for 3-5 days showed a lower risk of NEC (adjusted sHR 0.69, 95% CI [0.52, 0.94]; adjusted sHR 0.72, 95% CI [0.5, 1.03]), compared with those with No-IEAT. In the infants with low-risk EOS, there was no significant association between the duration of IEAT and the incidence of NEC. The RCS analysis showed a positive linear relationship between the duration of IEAT and the risk of NEC in very preterm infants at different EOS risk. Conclusions Competing-risk analysis showed that NEC risk may be inversely associated with short-term IEAT in the whole cohort and the non-low-risk EOS group. Notably, the risk of NEC tended to be higher with prolonged IEAT duration in very preterm infants at different EOS risk. These associational findings are exploratory and warrant further investigation.

Importance: The transition period from the delivery room to the neonatal intensive care unit (NICU) is critical for very preterm infants (VPIs) or very low birth weight (VLBW) infants, yet the association between physiological changes during transition period and early severe outcomes remains inadequately quantified. Objective: To investigate associations between physiological changes during transition period and early severe neonatal outcomes in VPIs or VLBW infants. Design: This cohort study utilized data from Chinese Neonatal Network (CHNN), prospectively collected from January 2019 to December 2023. Setting: National multicenter study. Participants: VPIs or VLBW infants with clear 5-minute APGAR score and the transport risk index of physiologic stability score (TRIPS) were included, and those admitted after the first day, discharged or transferred out within 7 days after birth, were excluded. Exposures: The exposure variable was a composite of the APGAR score and TRIPS. The APGAR score was analyzed as normal (7-10), low (0-6), and optimal (9-10). The TRIPS was grouped as low (0-10), intermediate (11-30), or high (>30). Main Outcome and Measures:The main outcome was a composite of early neonatal death and severe neurological injury (SNI). Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were estimated using generalized estimating equation models. Results: Of the 40391 included VPIs or VLBW infants, the composite outcome occurred in 4753 (11·77%) infants, including 2326 (5·76%) early neonatal deaths and 2680 (6·64%) SNIs. Increased TRIPS was associated with elevated risks of early severe neonatal outcomes across all APGAR categories. In optimal APGAR subgroup, composite outcome incidence per 1000 infants was 52 in low-TRIPS reference group, 100 in intermediate-TRIPS group (aOR: 1·42, 95% CI: 1·12-1·80), and 211 in high-TRIPS group (aOR: 1·80, 95% CI: 1·16-2·80). The initial deterioration (intermediate-TRIPS group) was characterized by high rates of hypothermia (71·6%) and need for invasive respiratory support (37·1%), whereas hypotension was nearly absent in intermediate-TRIPS group and emerged predominantly in high-TRIPS group. Conclusions and Relevance: The quality of management during transition period was associated with early severe neonatal outcomes, thus maintenance of normothermia and effective respiratory support represent initial clinical priorities to mitigate physiological deterioration and improve clinical outcomes.

[This corrects the article DOI: 10.3389/fped.2025.1632123.].

OBJECTIVES:To examine bronchopulmonary dysplasia (BPD) epidemiological data in Chinese very preterm infants and compare agreement between four diagnostic definitions and their predictive accuracy for discharge outcomes. DESIGN:Observational epidemiologic study of a multicentre cohort of the Chinese Neonatal Network (CHNN). SETTING:Tertiary neonatal intensive care units participating in the CHNN. PARTICIPANTS:42 664 preterm infants born at <32 weeks' gestational age from 2019 to 2023. MEASURES:BPD was diagnosed using four definitions: Shennan 1988, the National Institute of Child Health and Human Development (NICHD) 2001 and 2018, and the Neonatal Research Network (NRN) 2019 definitions. BPD prevalence and severity were examined. Agreement was assessed using kappa statistics. Predictive accuracy for discharge outcomes was evaluated using c-statistics from multivariable generalised estimating equation models. RESULTS:Among 42 664 infants (mean gestational age, 29.0 weeks; 43.1% females), BPD prevalence varied significantly: Shennan 1988: 37.0%, NICHD 2001: 51.1%, NICHD 2018: 37.0%, NRN 2019: 37.0%. NICHD 2001 and 2018 definitions classified more infants as severe BPD (16.4% and 10.1%, respectively), while NRN 2019 classified more as grade 2 (moderate; 15.0%). Shennan 1988 showed good agreement with NICHD 2018 (κ=1.0) and Jensen 2019 (κ=1.0). Shennan 1988 (c-statistic range: 0.921-0.974), NICHD 2018 (0.948-0.978) and NRN 2019 (0.949-0.982) demonstrated higher discriminative accuracy for discharge outcomes than NICHD 2001 (0.854-0.925). CONCLUSIONS:This study found a high prevalence of BPD among very preterm infants in China, varying by definitions. The Shennan 1988, NICHD 2018 and NRN 2019 definitions showed good agreement and better predictive accuracy for outcomes at discharge compared with NICHD 2001. These definitions could be prioritised for clinical use in our population.

Preterm infants face a heightened risk of various complications due to the immaturity of their physiological systems, with global rates of preterm birth increasing. These complications represent the leading causes of mortality in children. This review examines current research on the use of umbilical cord blood(UCB) for managing preterm complications, including bronchopulmonary dysplasia(BPD), hypoxic ischemic encephalopathy(HIE), necrotizing enterocolitis(NEC), sepsis and retinopathy of prematurity(ROP). UCB is rich in bioactive components, including hematopoietic stem cells(HSCs), mesenchymal stem cells(MSCs), and exosomes, which are crucial for neurological and vascular repair, anti-apoptosis, anti-inflammation, and immunomodulation. Both preclinical investigations and clinical trials have highlighted the potential of UCB therapy in mitigating the severity of preterm complications, enhancing clinical outcomes, and fostering long-term neural development. Current clinical studies aim to further confirm the safety and efficacy of UCB therapy, with future research concentrating on refining treatment protocols and tailoring personalized medical approaches to enhance the long-term well-being of preterm infants.

It is unclear whether there is an association between maternal abortion history and neonatal outcomes of singleton very preterm infants (VPIs). We assess the association between maternal abortion history and neonatal outcome of VPIs in China. All first parity singleton VPIs born at < 32 weeks gestational age (GA) who were admitted to neonatal intensive care units (NICU) participating in the Chinese Neonatal Network (CHNN) from 2019 to 2021 were included in the study. Multivariable logistic regression models were constructed to compare neonatal outcomes among infants with different maternal abortion histories after adjusting for confounders. A total of 7256 VPIs were included in this analysis. Overall, 3133 (43.2

Objective To evaluate the association between the timing of initial breastfeeding and the risk of necrotising enterocolitis (NEC) and other neonatal outcomes in very preterm infants (VPIs, <32 weeks’ gestation).Design Multicentre observational cohort study.Setting Data were collected from 102 tertiary neonatal intensive care units (NICUs) in China between 2019 and 2023 through the Chinese Neonatal Network.Patients A total of 12 679 VPIs admitted to NICUs within 24 hours of birth and initially breastfed within 7 days were included.Interventions Infants were categorised into four groups based on initial breastfeeding timing: within 24 hours (n=2242), 24–48 hours (n=3657), 48–72 hours (n=1870) and after 72 hours (n=4910, reference group).Main outcome measures The primary outcome was NEC (stage ≥2). Secondary outcomes included mortality, bronchopulmonary dysplasia, severe neurological injury, severe retinopathy of prematurity, late-onset sepsis, NICU length of stay and intravenous nutrition duration.Results Early breastfeeding initiation (<24 hours) was associated with a higher incidence of NEC (7.5% vs 4.3%, OR 1.92, 95% CI 1.21 to 3.06). No significant NEC risk increase was observed for feeding initiation after 24 hours. Early breastfeeding was linked to a shorter duration of intravenous nutrition (median 15 days (IQR 10–27) vs 22 days (IQR 14–33), mean difference −3.93 days, 95% CI −6.57 to −1.3). Subgroup analysis revealed increased NEC risk in neonates delivered via caesarean section, those receiving blood transfusions and those born <28 weeks’ gestation.Conclusions While early breastfeeding initiation (<24 hours) reduces intravenous nutrition duration, it may elevate NEC risk in specific high-risk subgroups. Feeding strategies should be individualised based on gestational age, delivery mode and transfusion status. Further randomised trials are needed to optimise early feeding protocols for VPIs.

INTRODUCTION:The impact of intrauterine growth status as measured by BW percentiles on retinopathy of prematurity (ROP) pathogenesis remains inadequately characterized. The objectives of the study were to establish BW percentile-specific risk gradients for ROP development. METHODS:A multicenter cohort study was conducted with data were collected from Chinese Neonatal Network between January, 2019 and December, 2021. The exposure was GA- and sex-specific BW percentile. The primary outcome was incidence of ROP. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, adjusted for potential confounders, and stratified by GA, infant sex, maternal hypertension, singleton/multiple birth. RESULTS:Totally 17,882 preterm infants were enrolled, BW was 1,300.0 (1,100.0-1,500.0) g and GA was 29.9 (28.6-31.0) weeks. The incidence was 27% for any stage ROP and 3.7% for severe ROP (stage 3 or above). Each decrease of BW percentile by 10% was associated with 15% increase of odds for either any stage ROP (aOR 0.85 [95% CI: 0.83-0.86]) or severe ROP (aOR 0.85 [95% CI: 0.82-0.89]). The optimal discriminative BW percentile on receiver operating characteristic curve was 26% for predicting any stage ROP and 19% for predicting severe ROP. Lower BW percentile under these cut-offs were associated with elevated odds of any stage ROP (aOR 2.20 [95% CI: 1.97-2.47] and severe ROP (aOR 2.91 [95% CI: 2.22-3.80]). CONCLUSIONS:ROP incidence was negatively associated with BW percentile. Each 10% decreased BW percentile was associated with 15% increased odds of any stage ROP and severe ROP.

INTRODUCTION:We aimed to evaluate whether the incidence of pneumothorax is associated with adverse neonatal outcomes in very preterm infants. METHODS:This multicenter cohort study included all infants with a gestational age of 24-31 weeks, admitted to the tertiary neonatal intensive care units of the Chinese Neonatal Network, from 2019 to 2022. Pneumothorax was diagnosed via chest X-ray or lung computed tomography. The primary outcome was a composite measure of mortality and/or any severe neonatal morbidity. Multivariable logistic or linear regression analyses were performed to assess the association between pneumothorax and neonatal outcomes. Propensity score matching was used to ensure the robustness of the results. RESULTS:Among the 37,917 infants in the study, 465 (1.2%) developed pneumothorax. Pneumothorax was significantly associated with a higher risk of mortality and/or severe neonatal morbidity (adjusted odds ratio = 3.15, 95% confidence interval: 2.36, 4.20). Pneumothorax exposure was also independently associated with increased mortality, severe intraventricular hemorrhage, moderate or severe bronchopulmonary dysplasia, and the need for invasive ventilation and its duration. Additionally, pneumothorax was associated with an increased length of hospital stay among survivors (adjusted odds ratio = 7.62, 95% confidence interval: 4.33, 10.91). The usage of high-frequency invasive mechanical ventilation before pneumothorax and pneumothorax treated with an intercostal chest drain seemed to have the most significant harmful effect (adjusted odds ratios were 3.34 and 3.27, respectively). CONCLUSION:Our study underscores the significant impact of pneumothorax on increasing mortality and severe morbidities in very preterm infants.

Antenatal corticosteroids (ACS) can improve the outcomes of preterm infants and have been widely adopted as the standard practice in managing pregnancies at high risk of preterm delivery between 22+0 and 33+6 weeks. Due to their significant benefit for the majority of pregnant women, several guidelines also state that maternal diabetes is not a contraindication for the use of ACS. However, no such evidence has been obtained from diabetic pregnancies. The Chinese Neonatal Network (CHNN), a national multicenter cohort study, recruited 31,915 very preterm infants (VPIs) from 79 NICUs. The outcomes were mortality and morbidity in hospital. Logistic regression models were employed to calculate the odds ratios (ORs) and its 95

Necrotising enterocolitis (NEC) is a significant complication for very preterm infants (VPIs). The role of genetic predisposition in the development of NEC among VPIs has not been firmly established. This study aimed to explore the heritability factors in NEC among VPIs. A retrospective cohort study was conducted on 4138 infants from 2069 twin pairs. Twins were categorised based on chorionicity.Chi-square analyses were conducted to compare the incidence of NEC between monochorionic and dichorionic twin pairs. The Pearson chi-square test and ACE modelling appropriate for analysing twin cohorts were utilised. Stratified analyses were conducted for early-onset and late-onset NEC, surgical NEC, and NEC in different gestational age groups. The overall incidence of NEC was 5

In the neonatal period, infectious diseases associated with high morbidity (e.g., neonatal sepsis and meningitis) are preliminarily assessed using indicators like C-reactive protein (CRP) and procalcitonin, but definitive diagnosis relies on pathogen detection through methods such as blood culture, which is time-consuming and has low sensitivity. To improve diagnostic efficiency, metagenomic next-generation sequencing (mNGS) is increasingly utilized, offering three testing modalities: DNA-only, RNA-only, and combined DNA+RNA channels. This retrospective study analyzed 894 clinical samples (peripheral blood, sputum, bronchoalveolar lavage fluid) to compare detection rates across channels. The overall mNGS positivity rate was 51.9% (464/894), with no significant differences among DNA-only (50.8%), RNA-only (55.7%), and combined channels (49.6%) (p > 0.05). Notably, bronchoalveolar lavage fluid samples exhibited the highest positivity rate (84.57%, 148/175), reaching 97.33% (73/75) with dual-channel testing. Sputum samples showed a 53.7% positivity rate (87/172), increasing to 82.35% (14/17) with dual-channel detection. Conversely, peripheral blood had an overall positivity rate of 43.14% (132/306), with the DNA-only channel outperforming RNA-only and dual channels (45.34% 5s. 43.00% and 34.21%). These findings underscore the importance of channel selection based on sample type to optimize diagnostic accuracy and cost-effectiveness.

Background There are emerging clinical evidence for umbilical cord blood mononuclear cells (UCBMNCs) intervention to improve preterm complications. The first critical step in cell therapy is to obtain high-quality cells. This retrospective study aimed to investigate the quantity and quality of UCBMNCs from very preterm infants (VPIs) for the purpose of autologous cell therapy in prevention and treatment of preterm complications. Methods Very preterm infants (VPIs) born in Guangdong Women and Children Hospital from January 1, 2017, to December 8, 2022, from whom cord blood was successfully collected and separated for public or private banking, were enrolled. The UCBMNCs characters from route cord blood tests performed in cord blood bank, impact of perinatal factors on UCBMNCs, the relationship between UCBMNCs characteristics and preterm outcomes, and the correlation of UCBMNCs characteristics and peripheral blood cells in VPIs were analyzed. Results Totally, 89 VPIs underwent UCB collection and processing successfully. The median cell number post processing was 2.6 × 10 8 . To infuse a dose of 5 × 10 7 cells/kg, only 3.4% of infants required a volume of more than 20 mL/kg, which exceeded the maximum safe volume limit for VPIs. However, when infusing 10 × 10 7 cells/kg, 25.8% of infants required a volume of more than 20 ml/kg volume. Antenatal glucocorticoids use and preeclampsia was associated with lower original UCBMNCs concentration. Both CD34+ hematopoietic stem cells (HSC) frequency and colony forming unit - granulocyte and macrophage (CFU-GM) number correlated negatively with gestational age (GA). UCBMNCs characters had no significant effect on preterm outcomes, whereas a significant positive correlation was observed between UCBMNCs concentration and total white blood cell, neutrophil, lymphocyte and PLT counts in peripheral blood. Conclusion UCBMNCs collected from VPIs was feasible for autologous cell therapy in improving preterm complications. Setting the infusion dose of 5 × 10 7 cells/kg guaranteed a safe infusion volume in more than 95% of the targeted infants. UCBMNCs characters did not affect preterm complications; however, the effect of UCBMNCs concentration on peripheral blood classification count should be considered when evaluating the immunomodulation of UCBMNCs transfusion.

ImportanceThe overutilization of antibiotics in very preterm infants (VPIs) at low risk of early-onset sepsis (EOS) is associated with increased mortality and morbidities. Nevertheless, the association of early antibiotic exposure with bronchopulmonary dysplasia (BPD) remains equivocal. ObjectiveTo evaluate the association of varying durations and types of early antibiotic exposure with the incidence of BPD in VPIs at low risk of EOS. Design, Setting, and ParticipantsThis national multicenter cohort study utilized data from the Chinese Neonatal Network (CHNN) which prospectively collected data from January 1, 2019, to December 31, 2021. VPIs less than 32 weeks' gestational age or with birth weight less than 1500 g at low risk of EOS, defined as those born via cesarean delivery, without labor or rupture of membranes, and no clinical evidence of chorioamnionitis, were included. Data analysis was conducted from October 2022 to December 2023. ExposureEarly antibiotic exposure was defined as the total number of calendar days antibiotics were administered within the first week of life, which were further categorized as no exposure, 1 to 4 days of exposure, and 5 to 7 days of exposure. Main Outcomes and MeasuresThe primary outcome was the composite of moderate to severe BPD or mortality at 36 weeks' post menstrual age (PMA). Logistic regression was employed to assess factors associated with BPD or mortality using 2 different models. ResultsOf the 27 176 VPIs included in the CHNN during the study period (14 874 male [54.7%] and 12 302 female [45.3%]), 6510 (23.9%; 3373 male [51.8%] and 3137 female [48.2.%]) were categorized as low risk for EOS. Among them, 1324 (20.3%) had no antibiotic exposure, 1134 (17.4%) received 1 to 4 days of antibiotics treatment, and 4052 (62.2%) received 5 to 7 days of antibiotics treatment. Of the 5186 VPIs who received antibiotics, 4098 (79.0%) received broad-spectrum antibiotics, 888 (17.1%) received narrow-spectrum antibiotics, and 200 (3.9%) received antifungals or other antibiotics. Prolonged exposure (5-7 days) was associated with increased likelihood of moderate to severe BPD or death (adjusted odds ratio [aOR], 1.23; 95% CI, 1.01-1.50). The use of broad-spectrum antibiotics (1-7 days) was also associated with a higher risk of moderate to severe BPD or death (aOR, 1.27; 95% CI, 1.04-1.55). Conclusions and RelevanceIn this cohort study of VPIs at low risk for EOS, exposure to prolonged or broad-spectrum antibiotics was associated with increased risk of developing moderate to severe BPD or mortality. These findings suggest that VPIs exposed to prolonged or broad-spectrum antibiotics early in life should be monitored for adverse outcomes.

GOALS:A combination of multiple tests was introduced to noninvasively investigate the differences in pathophysiologies among functional dyspepsia (FD) subgroups, including postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and overlap.BACKGROUND:It has not been extensively evaluated whether different pathophysiologies are involved in FD subgroups.STUDY:This multicenter study included 364 FD patients fulfilling Rome IV criteria and 47 healthy controls. A combined noninvasive gastric and autonomic function test was performed: The electrogastrogram and electrocardiogram were recorded simultaneously in the fasting state and after a drink test. Symptoms after drinking were recorded using visual analog scale.RESULTS:(1) Compared with HC, FD patients showed a decreased maximum tolerable volume (MTV) ( P <0.01) and percentage of normal gastric slow waves [normal gastric slow waves (%NSW)] ( P <0.01), and increased postdrinking symptoms, anxiety ( P <0.01), and depression ( P <0.01). The drink reduced %NSW in both FD patients and HC; however, the effect was more potent in patients. (2) The PDS and overlap groups displayed a reduced MTV ( P <0.05). The overlap group exhibited a higher symptom score at 30 minutes after drinking, and higher anxiety and depression scores, and a higher sympathovagal ratio than the EPS ( P <0.05 for all) and PDS ( P <0.01 for all). (3) In the PDS subgroup, the MTV, postprandial sympathovagal ratio, and depression were associated with the overall dyspepsia symptom scale (DSS, P =0.034, 0.021, 0.043, respectively). No significant associations were found in the other 2 subgroups.CONCLUSIONS:The combination of multiple tests can detect pathophysiological abnormities in FD patients. Overall, patients with overlap symptoms display more severe pathophysiologies.

Perinatal exposure of the neonatal lung to inflammation leads to decreased lung angiogenesis and the development of bronchopulmonary dysplasia (BPD). Notably, autologous cord blood mononuclear cells (ACBMNCs) can substantially prevent severe BPD and decrease the inflammatory response in surviving very preterm neonates. Angiopoietin-like protein 7 (Angptl7) is one of the main paracrine cytokines in cord blood stem cells, and is capable of stimulating human hematopoietic stem and progenitor cell expansion. The present study compared Angptl7 levels between the ACBMNCs infusion and control groups (cohort 1). Subsequently, the association between cord blood Angptl7 levels and BPD incidence in a cohort of very preterm neonates was assessed (cohort 2). The hypothesis was further verified in a lipopolysaccharide (LPS)-induced lung injury mouse model. The mRNA expression levels and protein concentrations of inflammatory cytokines in the lung tissue and mouse serum were measured using reverse transcription-quantitative PCR and ELISA, respectively. The number and diameter of lung vessels and macrophage infiltration were assessed using immunofluorescence staining. Compared with in the control group, Angptl7 levels were significantly higher in the ACBMNCs infusion group in cohort 1. In cohort 2, the cord blood Angptl7 levels were significantly lower in infants who later developed BPD. Multiple linear regression analysis showed that higher Angptl7 level was an independent protective factor for BPD. The concentrations of interleukin-6 and monocyte chemoattractant protein-1 were negatively correlated with cord blood Angptl7 level; whereas, vascular endothelial growth factor-A levels were positively correlated with Angptl7 levels. In the LPS-induced lung injury mouse model, the LPS group presented with a significant loss of pulmonary vessels and smaller vessel diameters, which were ameliorated in the Angptl7 treatment group. Furthermore, LPS-induced lung inflammation and macrophage infiltration were alleviated by Angptl7 treatment (P<0.05). In conclusion, the anti-inflammatory and proangiogenic effects of Angptl7 derived from cord blood stem cells may ameliorate BPD severity. The trial for cohort 1 was registered at ClinicalTrials.gov (trial registration no. NCT02999373; date registered, December 21, 2016).