Premature infants have a high risk of bronchopulmonary dysplasia (BPD), which is characterized by abnormal development of alveoli and pulmonary vessels. Exosomes and exosomal miRNAs (EXO-miRNAs) from bronchoalveolar lavage fluid are involved in the development of BPD and might serve as predictive biomarkers for BPD. However, the roles of exosomes and EXO-miRNAs from umbilical cord blood of BPD infants in regulating angiogenesis are yet to be elucidated. In this study, we showed that umbilical cord blood-derived exosomes from BPD infants impaired angiogenesis in vitro. Next-generation sequencing of EXO-miRNAs from preterm infants without (NBPD group) or with BPD (BPD group) uncovered a total of 418 differentially expressed (DE) EXO-miRNAs. These DE EXO-miRNAs were primarily enriched in cellular function-associated pathways including the PI3K/Akt and angiogenesis-related signaling pathways. Among those EXO-miRNAs which are associated with PI3K/Akt and angiogenesis-related signaling pathways, BPD reduced the expression of hsa-miR-103a-3p and hsa-miR-185-5p exhibiting the most significant reduction (14.3% and 23.1% of NBPD group, respectively); BPD increased hsa-miR-200a-3p expression by 2.64 folds of the NBPD group. Furthermore, overexpression of hsa-miR-103a-3p and hsa-miR-185-5p in normal human umbilical vein endothelial cells (HUVECs) significantly enhanced endothelial cell proliferation, tube formation, and cell migration, whereas overexpressing hsa-miR-200a-3p inhibited these cellular responses. This study demonstrates that exosomes derived from umbilical cord blood of BPD infants impair angiogenesis, possibly via DE EXO-miRNAs, which might contribute to the development of BPD.

Bronchopulmonary dysplasia (BPD) is a chronic, devastating disease primarily occurring in premature infants. To date, intervention strategies to prevent or treat BPD are limited. We aimed to determine the effects of umbilical cord blood‐derived exosomes (UCB‐EXOs) from healthy term pregnancies on hyperoxia‐induced lung injury and to identify potential targets for BPD intervention. A mouse model of hyperoxia‐induced lung injury was created by exposing neonatal mice to hyperoxia after birth until the 14th day post birth. Age‐matched neonatal mice were exposed to normoxia as the control. Hyperoxia‐induced lung injury mice were intraperitoneally injected with UCB‐EXO or vehicle daily for 3 days, starting on day 4 post birth. Human umbilical vein endothelial cells (HUVECs) were insulted with hyperoxia to establish an in vitro model of BPD to investigate angiogenesis dysfunction. Our results showed that UCB‐EXO alleviated lung injuries in hyperoxia‐insulted mice by reducing histopathological grade and collagen contents in the lung tissues. UCB‐EXO also promoted vascular growth and increased miR‐185‐5p levels in the lungs of hyperoxia‐insulted mice. Additionally, we found that UCB‐EXO elevated miR‐185‐5p levels in HUVECs. MiR‐185‐5p overexpression inhibited cell apoptosis, whereas promoted cell migration in HUVECs exposed to hyperoxia. The luciferase reporter assay results revealed that miR‐185‐5p directly targeted cyclin‐dependent kinase 6 (CDK6), which was downregulated in the lungs of hyperoxia‐insulted mice. Together, these data suggest that UCB‐EXO from healthy term pregnancies protect against hyperoxia‐induced lung injuries via promoting neonatal pulmonary angiogenesis partially by elevating miR‐185‐5p.

Mesenchymal stem cells (MSCs) have been shown as an effective medicinal means to treat bronchopulmonary dysplasia (BPD). The widely used MSCs were from Wharton's jelly of umbilical cord (UC‐MSCs) and bone marrow (BM‐MSCs). Amniotic fluid MSCs (AF‐MSCs) may be produced before an individual is born to treat foetal diseases by autoplastic transplantation. We evaluated intratracheal (IT) MSCs as an approach to treat an hyperoxia‐induced BPD animal model and compared the therapeutic effects between AF‐, UC‐ and BM‐MSCs. A BPD animal model was generated by exposing newborn rats to 95% O₂. The continued stress lasted 21 days, and the treatment of IT MSCs was conducted for 4 days. The therapeutic effects were analysed, including lung histology, level of inflammatory cytokines, cell death ratio and state of angiogenesis, by sacrificing the experimental animal at day 21. The lasting hyperoxia stress induced BPD similar to the biological phenotype. The treatment of IT MSCs was safe without deaths and normal organ histopathology. Specifically, the treatment was effective by inhibiting the alveolar dilatation, reducing inflammatory cytokines, inducing angiogenesis and lowering the cell death ratio. AF‐MSCs had better therapeutic effects compared with UC‐MSCs in relieving the pulmonary alveoli histological changes and promoting neovascularization, and UC‐MSCs had the best immunosuppressive effect in plasma and lung lysis compared with AF‐MSCs and BM‐MSCs. This study demonstrated the therapeutic effects of AF‐, UC‐ and BM‐MSCs in BPD model. Superior treatment effect was provided by antenatal MSCs compared to BM‐MSC in a statistical comparison.

Background: The first 1000 days of life, encompassing pregnancy and the first 2 years after birth, represent a critical period for human health development. Despite this significance, there has been limited research into the associations between mixed exposure to air pollutants during this period and the development of asthma/wheezing in children. Furthermore, the finer sensitivity window of exposure during this crucial developmental phase remains unclear. Objective: This study aims to assess the relationships between prenatal and postnatal exposures to various ambient air pollutants (particulate matter 2.5 [PM2.5], carbon monoxide [CO], sulfur dioxide [SO2], nitrogen dioxide [NO2], and ozone [O3]) and the incidence of childhood asthma/wheezing. In addition, we aimed to pinpoint the potential sensitivity window during which air pollution exerts its effects. Methods: We conducted a prospective birth cohort study wherein pregnant women were recruited during early pregnancy and followed up along with their children. Information regarding maternal and child characteristics was collected through questionnaires during each round of investigation. Diagnosis of asthma/wheezing was obtained from children’s medical records. In addition, maternal and child exposures to air pollutants (PM2.5 CO, SO2, NO2, and O3) were evaluated using a spatiotemporal land use regression model. To estimate the mutual associations of exposure to mixed air pollutants with the risk of asthma/wheezing in children, we used the quantile g-computation model. Results: In our study cohort of 3725 children, 392 (10.52%) were diagnosed with asthma/wheezing. After the follow-up period, the mean age of the children was 3.2 (SD 0.8) years, and a total of 14,982 person-years were successfully followed up for all study participants. We found that each quartile increase in exposure to mixed air pollutants (PM2.5, CO, SO2, NO2, and O3) during the second trimester of pregnancy was associated with an adjusted hazard ratio (HR) of 1.24 (95% CI 1.04-1.47). Notably, CO made the largest positive contribution (64.28%) to the mutual effect. After categorizing the exposure according to the embryonic respiratory development stages, we observed that each additional quartile of mixed exposure to air pollutants during the pseudoglandular and canalicular stages was associated with HRs of 1.24 (95% CI 1.03-1.51) and 1.23 (95% CI 1.01-1.51), respectively. Moreover, for the first year and first 2 years after birth, each quartile increment of exposure to mixed air pollutants was associated with HRs of 1.65 (95% CI 1.30-2.10) and 2.53 (95% CI 2.16-2.97), respectively. Notably, SO2 made the largest positive contribution in both phases, accounting for 50.30% and 74.70% of the association, respectively. Conclusions: Exposure to elevated levels of mixed air pollutants during the first 1000 days of life appears to elevate the risk of childhood asthma/wheezing. Specifically, the second trimester, especially during the pseudoglandular and canalicular stages, and the initial 2 years after birth emerge as crucial susceptibility windows. Trial Registration: Chinese Clinical Trial Registry ChiCTR-ROC-17013496; https://tinyurl.com/2ctufw8n

Twin pregnancies have a higher risk of preterm birth (PTB) than single pregnancies, but studies about prenatal air pollution exposure and PTB in twin pregnancies are still scarce. To explore associations of prenatal fine particulate matter (PM_2.5) exposure with PTB in twins, we collected birth data from 21 hospitals across China. Data on PM_2.5 and its compositions (NO₃⁻, BC, NH₄⁺, SO₄²⁻, and OM) were collected from Tracking Air Pollution. Generalized linear models were used to examine associations of air pollution with PTB. Each IQR increment in PM_2.5, NH₄⁺, SO₄²⁻, NO₃⁻, BC, and OM during entire pregnancy, the OR (95% CI) were 1.46 (1.34–1.59), 1.54 (1.39–1.70), 1.34 (1.25–1.44), 1.44 (1.30–1.59), 1.28 (1.20–1.37), and 1.28 (1.18–1.38), respectively. The results of trimester-specific analyses followed the patterns as seen during the entire pregnancy (all p < 0.05). The PAF of PTB attributable to PM_2.5 was 40.75% (95% CI: 32.5%, 48.26%) in the total population. Participants living in warmer regions and lower residential greenness were more susceptible to PM_2.5. Our findings suggest pregnant women should avoid severe air pollution exposure throughout pregnancy. Reducing heat exposure and increasing green spaces in communities can reduce PTB risk.

Introduction: Since December 2012, the prophylactic use of caffeine to treat AOP in preterm infants has been approved in China. This study aimed to investigate the relationship between early caffeine treatment initiation and the incidence of oxygen radical diseases in neonatology (ORDIN) in Chinese preterm infants.Methods: A retrospective study was conducted at two hospitals in South China, involving 452 preterm infants with gestational ages less than 37 weeks. The infants were divided into early (227 cases, initiating within 48 h after birth) and late (225 cases, initiating over 48 h after birth) caffeine treatment group. Logistic regression analysis and Receiver Operating Characteristic (ROC) curves were used to evaluate the association between early caffeine treatment and the incidence of ORDIN.Results: The results showed that extremely preterm infants in early treatment group had a lower incidence of PIVH and ROP compared to those in the late treatment group (PIVH, 20.1% versus 47.8%, P = 0.02; ROP, 70.8% versus 89.9%, P = 0.025). Very preterm infants in the early treatment group had a lower incidence of BPD and PIVH compared to those in the late treatment group (BPD, 43.8% versus 63.1%, P = 0.002; PIVH, 9.0% versus 22.3%, P = 0.001). Moreover, VLBW infants who received early caffeine treatment exhibited a decreased incidence of BPD (55.9% versus 80.9%, P = 0.000), PIVH (11.8% versus 33.1%, P = 0.000), and ROP (69.9% versus 79.8%, P = 0.043) compared to those in the late treatment group. Infants in the early caffeine treatment showed a reduced likelihood of PIVH (adjusted odds ratio, 0.407; 95%CI, 0.188–0.846) but did not exhibit a significant association with other terms of ORDIN. ROC analysis revealed that early initiation of caffeine treatment was associated with lower risk of BPD, PIVH, and ROP in preterm infants.Discussion: In conclusion, this study demonstrates that early initiation of caffeine treatment is associated with a decreased incidence of PIVH in Chinese preterm infants. Further prospective investigations are necessary to verify and elucidate the precise effects of early caffeine treatment on complications in preterm Chinese infants.