Ureaplasma urealyticum and Clinical Outcomes in Extremely Premature Infants: A Single-Center Retrospective Analysis

Ureaplasma urealyticum and Clinical Outcomes in Extremely Premature Infants: A Single-Center Retrospective Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Ureaplasma urealyticum and Clinical Outcomes in Extremely Premature Infants: A Single-Center Retrospective Analysis YaBo Mei, XinYang Jiang, HuaYu Liang, ShuMei Wang, Feng Wang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8839125/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Background Ureaplasma urealyticum (Uu) colonization is associated with an increased risk of preterm birth. However, whether postnatal Uu colonization in extremely preterm infants affects clinical outcomes—particularly bronchopulmonary dysplasia (BPD)-remains inconsistent in current evidence, with limited domestic research available. Methods This retrospective study included extremely preterm infants admitted to the neonatal intensive care unit between January 2019 and June 2023, who underwent Uu culture via pharyngeal swab within 6 hours after birth (within 2 hours after admission). Infants were divided into Uu-positive and Uu-negative groups based on culture results. Perinatal data and clinical outcomes were collected, and multiple regression analysis was performed to examine the independent association between Uu positivity and BPD, as well as other major outcomes. Results A total of 70 extremely preterm infants were included, of whom 46 (65.7%) required oxygen supplementation at a postmenstrual age of 36 weeks, meeting the diagnostic criteria for BPD. The proportion of infants delivered vaginally was significantly higher in the Uu-positive group than in the Uu-negative group (91.18% vs. 61.11%, P = 0.003). The duration of invasive mechanical ventilation was longer in the Uu-positive group (P = 0.002). Linear regression indicated that both gestational age at birth and Uu positivity significantly influenced the duration of invasive ventilation. However, after adjusting for confounders such as gestational age, birth weight, and mode of delivery in multiple regression analysis, postnatal Uu positivity via pharyngeal swab was not identified as an independent risk factor for BPD. Conclusion Vaginal delivery may increase the risk of postnatal Uu colonization in the respiratory tract of extremely preterm infants. Uu colonization is associated with a longer duration of invasive mechanical ventilation, but this study did not confirm it as an independent risk factor for BPD. Future studies with larger sample sizes and prospective designs are needed to further clarify the role of Uu in lung development in extremely preterm infants. Health sciences/Diseases Health sciences/Health care Health sciences/Medical research extremely preterm infants Ureaplasma urealyticum bronchopulmonary dysplasia Figures Figure 1 Introduction Ureaplasma species are common colonizers and opportunistic pathogens in the neonatal period 1 , 2 . A large-scale epidemiological survey in China revealed that among hospitalized newborns with detected Ureaplasma urealyticum (Uu) positivity, up to 93.99% were within the neonatal age range, indicating that Uu represents a clinically significant microorganism in this vulnerable population 2 . This finding is particularly pronounced in preterm infants: the rate of Uu positivity in very preterm infants born before 26 weeks of gestation can reach approximately 65% 3 . The association between Uu and adverse outcomes in preterm infants-especially bronchopulmonary dysplasia (BPD)-has long been a major focus in neonatology 4 – 11 . Numerous retrospective studies have reported a significantly higher incidence of BPD in Uu-positive preterm infants compared with Uu-negative controls 1 , 9 , 10 , 12 – 14 . The underlying pathological mechanism is believed to involve a persistent pulmonary inflammatory response induced by Uu, which plays a central role in the development and progression of BPD 1 , 3 , 10 – 12 , 15 – 17 . However, existing clinical evidence remains contradictory: multiple studies have reported inconsistent findings regarding the association between Uu and BPD risk 3 , 6 , 10 , 11 , 18 – 20 . This heterogeneity may arise from variations across studies in baseline infant characteristics such as gestational age and birth weight, differences in diagnostic criteria for BPD, and insufficient differentiation in the timing of Uu detection, colonization sites, and strain virulence. Furthermore, most prior studies have analyzed preterm infants as a broad, heterogeneous group, failing to adequately delineate the independent impact of Uu in the specific subpopulation of extremely preterm infants, who exhibit particularly intense inflammatory responses and extreme organ immaturity 3 , 21 , 22 . Previous research has shown that in cases of preterm premature rupture of membranes (PPROM) with Uu amniotic infection, an earlier gestational age at membrane rupture is associated with a stronger intra-amniotic inflammatory response 21 . This suggests that in extremely preterm infants, Uu colonization or infection may trigger an amplified inflammatory cascade, thereby exacerbating injury to developing organ systems, including the lungs. Given the high prevalence of Uu in extremely preterm infants, its potential to intensify inflammatory states, and the compounded risk resulting from the inherent vulnerability of this population, clarifying the independent effect of Uu positivity on comprehensive clinical outcomes-such as BPD severity, other preterm-related complications, and mortality-is crucial for improving clinical management and prognosis. Nevertheless, high-quality studies systematically examining the relationship between Uu colonization status and multidimensional clinical outcomes in extremely preterm infants remain scarce. Therefore, this study aims to conduct a retrospective cohort analysis, rigorously controlling for key confounders such as gestational age and birth weight, to investigate whether Uu positivity is associated with short-term major clinical outcomes among extremely preterm infants treated in neonatal intensive care units in China. Outcomes of interest include BPD, sepsis, retinopathy of prematurity, in-hospital mortality, and others. This work intends to provide an evidence-based foundation for refined risk stratification and optimized timing of interventions in this high-risk population. Materials and Methods Study Design and Population This retrospective cohort study included infants admitted to a tertiary neonatal intensive care unit (NICU) in Northern China (January 2019-June 2023) with GA < 28 weeks, intubation within 6 hours of birth, and nasopharyngeal Uu culture within 2 hours of NICU admission. Uu culture was performed semiquantitatively using a mycoplasma isolation kit (Zhuhai DL Biotechnology). The study adhered to the Declaration of Helsinki and was approved by the institutional ethics board. Waiver of informed consent was granted per national regulations for retrospective studies. Outcomes The primary outcome was BPD, defined as oxygen requirement at 36 weeks’ postmenstrual age 23 . Secondary outcomes included mortality, palliative care, ROP, durations of invasive/non-invasive ventilation, oxygen therapy, total respiratory support, and hospitalization. Statistical Analysis The sample size was estimated based on a previous study 14 , in which the BPD incidence was approximately 78% in very low birth weight infants with maternal Ureaplasma colonization, compared to 43% in those without colonization. With 80% power and α = 0.05, a sample size of > 25 infants per group was sufficient to detect significant differences. Continuous variables were summarized by mean (range) or median (IQR), and categorical variables were described using count (percentage). Comparison among each group were done by Chi-square test, Fisher’s exact test, Mann-Whitney U test or independent t test. Relationships between variables and duration of treatment were analyzed by fitting linear regression models with 95% CI; model significance was evaluated by analysis of variance. All analyses were conducted using SPSS (Version 26). Variates with a P-value < 0.1 were included in the multivariate logistic analysis. Multivariate analysis was performed by binary logistic regression and odds ratios (OR) and 95% confidence intervals (CI) were calculated. Statistical significance was accepted at P < 0.05. Results 1.Study Population During the study period, 292 preterm infants were admitted to the NICU within 72 hours of birth. Among these, 91 infants (31.2%) underwent Uu pharyngeal swab culture. Twelve infants were excluded due to gestational age (GA) ≥ 28 weeks, and 9 were excluded for incomplete data. A total of 70 infants were included in the final analysis, with Uu-positive (n = 34, 48.57%) and Uu-negative (n = 36, 51.43%) groups defined based on culture results (Fig. 1 ). Of these, 65.71% (46/70) developed BPD. The baseline clinical characteristics of the cohort are summarized in Table 1 . 2. Baseline Characteristics No significant differences were observed between the Uu-positive and control groups in gestational age (weeks, GA), birth weight, sex, singleton status, in vitro fertilization (IVF) rates, antenatal steroid/antibiotic use, macrolide prophylaxis, preterm premature rupture of membranes (PPROM), histologic chorioamnionitis, maternal age, 6-hour postnatal complete blood count (white blood cells, platelets, hemoglobin), Apgar scores (1- and 5-minute), or surfactant administration (all P > 0.05). However, the Uu-positive group had a significantly higher proportion of vaginally delivered infants ( P = 0.003) (Table 1 ). Table 1 Clinical characteristics stratified by Ureaplasma Colonization status Characteristic Ureaplasma p value Positive group Control group (n = 34) (n = 36) Gestational age (weeks), median (IQR) 26.03 (23.14, 27.86) 26.50 (23.00, 27.86) 0.057 Birth weight (g), mean (range) 880.44 (570.00, 1290.00) 950.00 (600.00, 1260.00) 0.115 Sex (male), n (%) 22 (64.71) 24 (66.67) 0.863 Singleton, n (%) 23 (67.65) 22 (61.11) 0.568 In vitro fertilization (IVF) offspring, n (%) 18 (52.94) 19 (52.78) 0.989 Antenatal steroids, n (%) 32 (94.12) 35 (97.22) 0.609 Antenatal antibiotics, n (%) 16 (47.01) 21 (58.33) 0.345 Antenatal macrolides, n (%) 2 (5.88) 1 (2.78) 0.609 PPROM > 12 h, n (%) 14 (41.18) 14 (38.89) 0.839 Histologic chorioamnionitis,n (%) 28 (82.35) 28 (77.78) 0.632 Vaginal delivery, n(%) 31 (91.18) 22 (61.11) 0.003 Maternal age (median (IQR)) 32.50 (27.00-35.25) 33.00 (29.25–36.75) 0.617 Leukocyte count, ×109/l(Median (IQR)) 19.05 (8.28–35.32) 14.18 (8.16–24.17) 0.398 platelet count, (Mean ± SD) 206.00 ± 63.61 239.00 ± 66.48 0.057 Hgb count, (Mean ± SD) 147.71 ± 22.30 152.74 ± 24.27 0.412 1 min Apgar Score, median (IQR) 7.50 (5.75-8.00) 8.00 (6.00–8.00) 0.314 5 min Apgar Score, median (IQR) 9.00 (7.75-9.00) 9.00 (8.00–10.00) 0.382 Surfactant (any dose), n (%) 32 (94.12) 34 (94.44) 1.000 PROM Prelabour rupture of the membrane 3. Secondary Outcomes 3.As shown in Table 2 , the two groups did not differ significantly in: Duration of hospitalization, clinically significant patent ductus arteriosus (PDA, requiring medical/surgical intervention), IVH, PVL, NEC, ROP, EUGR, Late-onset sepsis, meningitis, Death prior to discharge, Deafness or suspected deafness, persistent pulmonary arterial hypertension(PPHN), fungal infections, Using NO, Duration of peripheral venous nutrition, or using of vasoactive drugs (all P > 0.05). Table 2 Primary and secondary outcomes by colonization status Outcome Ureaplasma p value Positive group Control group (n = 34) (n = 36) Duration of hospitalization, days, median (IQR) 112.00 (90.00-129.75) 94.00 (84.00-112.75) 0.076 PDA requiring treatment (drug), n (%) 14 (41.18) 18 (50.00) 0.459 PDA requiring treatment (ligation), n (%) 2 (5.88) 2 (55.56) 1.000 IVH ≥ grade 3, n (%) 15 (44.12) 11 (30.56) 0.241 PVL ≥ stage 2, n (%) 3 (8.82) 4 (11.11) 1.000 NEC ≥ stage 2, n (%) 5 (14.71) 3 (8.33) 0.472 ROP ≥ stage 3, n (%) 7 (20.59) 15 (41.67) 0.069 EUGR, n (%) 7 (20.59) 7 (19.44) 0.905 Late onset sepsis, n (%) 19 (55.88) 15 (41.67) 0.234 Meningitis, n (%) 7 (20.59) 6 (16.67) 0.673 Death prior to discharge, n (%) 2 (5.88) 2 (5.56) 1.000 Deafness or suspected deafness, N (%) 3 (8.82) 3 (8.33) 1.000 PPHN, n (%) 25 (73.53) 23 (63.89) 0.462 fungal infection, n (%) 3 (8.82) 0 (0.00) 0.114 Using NO, n (%) 6 (17.65) 5 (13.89) 0.703 Duration of peripheral venous nutrition, days, mean ± SD 45.70 ± 22.16 40.89 ± 14.69 0.293 using of vasoactive drugs(≤7 days), n (%) 15 (44.12) 9 (25.00) 0.105 ROP Retinopathy of prematurity, BPD Bronchopulmonary dysplasia, IVH Intraventricular hemorrhage, NEC necrotizing enterocolitis, EUGR extrauterine growth restriction, PVL Periventricular leukomalacia. 4. Respiratory Outcomes Comparative analysis of respiratory outcomes revealed that the Uu-positive group required significantly longer invasive ventilation ( P = 0.002). No differences were observed in BPD severity grades, duration of oxygen therapy, non-invasive ventilation, total respiratory support, rates or duration of dexamethasone treatment (all P > 0.05) (Table 3 ). Table 3 BPD and respiratory support stratified by Ureaplasma colonization status BPD Ureaplasma p value Positive group Control group (n = 34) (n = 36) BPD, n (%) 24 (70.59) 22 (61.11) 0.404 BPD(Grade ≥ 2), n (%) 16 (47.06) 10 (27.78) 0.095 BPD(Grade>2), n (%) 5 (14.71) 1 (2.78) 0.102 Duration of invasive ventilation, days, median (IQR) 32.00 (12.50–41.00) 10.00 (5.25–24.75) 0.002 Duration of non-invasive ventilation, days, median (IQR) 42.00 (31.00-54.50) 40.00 (23.00-44.75) 0.242 Duration supplemental oxygen, days, median (IQR) 9.00 (3.75–18.50) 14.00 (6.25-28.00) 0.129 Duration of total respiratory support, days, median (IQR) 80.00 (63.75–105.00) 69.00 (55.75–86.50) 0.054 Dexamethasone, n (%) 16 (47.06) 13 (36.11) 0.353 Duration of Dexamethasone, days, median (IQR) 1.00 (0.00–10.00) 0.00 (0.00-9.75) 0.382 5. Multivariate Analysis for BPD Given BPD's multifactorial etiology, we evaluated whether Uu colonization independently contributed to BPD. Variables with P < 0.05 in univariate analysis (GA, sex, PDA treatment) were included in the logistic regression model. Stepwise regression identified only GA ( P = 0.026) and male sex ( P = 0.009) as independent BPD risk factors. Uu colonization showed no significant association (this factor did not meet the entry criteria for regression analysis) (Table 4 ). Table 4 Multivariate logistic analysis of factors associated with BPD Variates BPD(n = 46) no BPD(n = 24) Adjusted OR (95% CI) p-Value Gestational age (weeks), median (IQR) 26.14 (25.00–27.00) 27.07 (26.14–27.68) 0.533 (0.307, 0.926) 0.026 Sex (male), male, n (%) 34 (73.91) 12 (50.00) 6.032 (1.558, 23.353) 0.009 PDA requiring treatment (drug and ligation), n (%) 26 (56.52) 9 (37.50) 0.283 (0.078, 1.026) 0.055 Discussion This retrospective study found that: 1) The positive rate of early postnatal Uu culture via pharyngeal swab was significantly higher in extremely preterm infants delivered vaginally compared to those delivered by cesarean section; 2) After adjusting for confounders, early postnatal Uu positivity was not an independent risk factor for BPD in extremely preterm infants, nor did it significantly increase the risk of other severe complications (such as ROP, sepsis) or total hospital stay; 3) Uu positivity was independently associated with a longer duration of invasive mechanical ventilation. The higher rate of Uu positivity in vaginally delivered infants in this study aligns with the established understanding that Uu is primarily transmitted through vertical mother-to-child transmission 24 . Epidemiological surveys indicate that the vertical transmission rate from Uu-infected mothers to their neonates can range from 18% to 88% 1,24 . Uu detection is significantly associated with vaginal delivery and maternal genital tract colonization, supporting the notion that exposure during delivery is the primary route of neonatal acquisition 11 .This finding has clinical implications: given the association between maternal genital Uu infection and adverse pregnancy outcomes such as chorioamnionitis, preterm premature rupture of membranes, and preterm birth 25 , 26 , future research could explore the potential value of perinatal Uu screening in high-risk pregnant populations. Numerous studies have reported an epidemiological link between Uu and BPD in preterm infants 2 , 8 , 27 . This study also observed that Uu-positive infants required longer invasive respiratory support 6 , suggesting that Uu colonization may exacerbate airway inflammation and injury. This is consistent with the previous view that Uu can induce pulmonary inflammatory responses and increase oxygen dependency 1 , 3 , 10 , 12 , 25 . Autopsy studies have also found more pronounced pulmonary fibrosis and inflammatory cell infiltration in very low birth weight infants with Uu infection 28 , 29 . However, this apparent association often diminishes or disappears after controlling for confounding factors. For example, Chen et al. found that after adjusting for variables such as gestational age, the association between Uu-related pneumonia and BPD lost statistical significance 6 . A Polish study similarly suggested that Uu exposure only increased the risk of BPD when coexisting with prolonged mechanical ventilation 11 . The multiple regression analysis in this study led to a similar conclusion: gestational age at birth and sex were independent risk factors for BPD, whereas postnatal Uu positivity via pharyngeal swab was not an independent predictor.This collective evidence underscores the complexity of the Uu-BPD relationship: their association may be confounded or modified by various factors including gestational age, duration of mechanical ventilation, definition of infection (colonization vs. invasive infection), and strain virulence. Given the association between Uu colonization and prolonged ventilation, eradicating Uu might theoretically improve outcomes. However, recent high-quality randomized controlled trials (such as the AZTEC trial) have shown that postnatal prophylactic use of azithromycin neither reduces the incidence of BPD nor improves long-term neurodevelopmental outcomes 18 , 19 , 30 . These negative results compel a reassessment of the critical time window for Uu-induced lung injury. Growing evidence points to the pivotal role of prenatal intrauterine exposure 17 , 21 , 22 , 25 , 31 , 32 .Studies indicate that intra-amniotic Uu infection (but not infection with other microorganisms or inflammation alone) is independently associated with an increased risk of BPD 32 . Furthermore, obstetric research suggests that the benefit of azithromycin in improving outcomes for extremely preterm infants may be mediated primarily by influencing the intrauterine infection milieu rather than treating the neonate 2 , 9 , 13 , 19 , 27 , 31 , 33 .This hypothesis is supported by pathological findings: in analyses of causes of death in preterm infants, Uu is the most frequently detected microorganism in placental/membrane tissues, yet its detection rate in fetal/neonatal parenchymal tissues is much lower 34 . This implies that Uu invasion of the fetal membranes, triggering an intrauterine inflammatory response, may be the primary mechanism leading to altered fetal lung development programming and increased BPD risk, whereas postnatal respiratory tract colonization might merely be a continuation or a secondary marker of this process. This study has several limitations. First, as a retrospective analysis, data on maternal genital tract Uu colonization status and placental/amniotic fluid pathology were unavailable for all infants, making it difficult to distinguish between intrauterine infection and postnatal colonization. Second, during the study period, pharyngeal swab culture was routinely performed only on intubated infants, potentially introducing selection bias. Finally, the relatively small sample size may have limited the power to detect subtle effect differences. In summary, this study found that vaginal delivery significantly increases the risk of postnatal respiratory Uu colonization in extremely preterm infants, and that Uu colonization is independently associated with prolonged invasive ventilation.However, it did not confirm Uu colonization as an independent risk factor for BPD. Integrating recent clinical trial data and mechanistic research, we hypothesize that the inflammatory environment induced by prenatal intrauterine Uu exposure, rather than mere postnatal colonization, may be the key driver in the pathogenesis of BPD. Future research should employ prospective designs, combine assays of maternal genital tract, placental, amniotic fluid, and serial neonatal samples, and incorporate microbial virulence analysis to more precisely elucidate the exact role of Uu in preterm lung development and to provide a basis for targeted prenatal intervention strategies. Abbreviations BPD Bronchopulmonary dysplasia EUGR extrauterine growth restriction GA gestational age IVF vitro fertilization IVH Intraventricular hemorrhage NEC necrotizing enterocolitis NICU neonatal intensive care unit PDA patent ductus arteriosus PPHN persistent pulmonary arterial hypertension PPROM preterm premature rupture of membranes PVL Periventricular leukomalacia ROP Retinopathy of prematurity Uu Ureaplasma urealyticum Declarations Clinical trial number: not applicable Ethics approval and consent to participate The study adhered to the Declaration of Helsinki and was approved by the institutional ethics board. The retrospective study was approved by the Ethics Committee of the Seventh Medical Center of the Chinese PLA General Hospital. Waiver of informed consent was granted per national regulations for retrospective studies. Consent for publication Not applicable Funding: This work was supported by the National Key Research and Development Program of China (2021YFC2701701). Author Contribution YM and ZF designed the research, XH analyzed the data, YM and QL wrote the manuscript; HL, SW and ZC analyzed and interpreted the data; QL and ZF designed the research, analyzed the data, and corrected the manuscript. Acknowledgements No. Data Availability The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. References Venturelli, N., Zeis, A., De Beritto, T. & Hageman, J. R. Ureasplasma and Its Role in Adverse Perinatal Outcomes: A Review. NeoReviews 22 (9), e574–e584. 10.1542/neo.22-9-e574 (2021). Huang, M. et al. long, lin, Epidemiological characteristics and clinical antibiotic resistance analysis of Ureaplasma urealyticum infection among women and children in southwest China. BMC Infect Dis . ;24:849. (2024). 10.1186/s12879-024-09760-9 Viscardi, R. M. & Kallapur, S. G. Role of Ureaplasma Respiratory Tract Colonization in Bronchopulmonary Dysplasia Pathogenesis. Clin. 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Pulmonary vascular and alveolar development in preterm lambs chronically colonized with Ureaplasma parvum. Am. J. Physiol-Lung Cell. Mol. Physiol. 299 (2), L232–L241. 10.1152/ajplung.00369.2009 (2010). Viscardi, R. M. et al. Randomised trial of azithromycin to eradicate Ureaplasma in preterm infants. Arch. Dis. Child. - Fetal Neonatal Ed. 105 (6), 615–622. 10.1136/archdischild-2019-318122 (2020). Motomura, K. et al. Intra-Amniotic Infection with Ureaplasma parvum Causes Preterm Birth and Neonatal Mortality That Are Prevented by Treatment with Clarithromycin. Ballard JD, ed. mBio . ;11(3):e00797-20. (2020). 10.1128/mBio.00797-20 Prenatal exposure to intra-amniotic infection with Ureaplasma species increases the prevalence of bronchopulmonary dysplasia. Accessed January 31. (2026). https://www.tandfonline.com/doi/epdf/10.1080/14767058.2024.2320670?needAccess=true Matasariu, D. et al. Genital infection with Ureaplasma urealyticum and its effect on pregnancy. Exp. Ther. Med. 23 (1), 89. 10.3892/etm.2021.11012 (2021). Ghanchi, N. K. et al. Pathogens Identified by Minimally Invasive Tissue Sampling in India and Pakistan From Preterm Neonatal Deaths: The PURPOSE Study. Clin. Infect. Dis. 76 (3), e1004–e1011. 10.1093/cid/ciac747 (2023). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 07 May, 2026 Reviews received at journal 06 May, 2026 Reviewers agreed at journal 28 Apr, 2026 Reviews received at journal 06 Apr, 2026 Reviewers agreed at journal 02 Apr, 2026 Reviewers agreed at journal 31 Mar, 2026 Reviewers invited by journal 13 Feb, 2026 Editor invited by journal 13 Feb, 2026 Editor assigned by journal 11 Feb, 2026 Submission checks completed at journal 11 Feb, 2026 First submitted to journal 10 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8839125","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":591706348,"identity":"03816c26-a2db-4292-86dd-bb5b4bd8e5b0","order_by":0,"name":"YaBo Mei","email":"","orcid":"","institution":"Department of Neonatology, Faculty of Pediatrics, Seventh Medical Center of PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"YaBo","middleName":"","lastName":"Mei","suffix":""},{"id":591706349,"identity":"22b2398f-c5b4-4250-8e81-ad2568e080cd","order_by":1,"name":"XinYang Jiang","email":"","orcid":"","institution":"Department of Neonatology, Faculty of Pediatrics, Seventh Medical Center of PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"XinYang","middleName":"","lastName":"Jiang","suffix":""},{"id":591706350,"identity":"fa7f3682-d846-4eaf-91c4-cbfe791ec49c","order_by":2,"name":"HuaYu Liang","email":"","orcid":"","institution":"Department of Neonatology, Faculty of Pediatrics, Seventh Medical Center of PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"HuaYu","middleName":"","lastName":"Liang","suffix":""},{"id":591706351,"identity":"0bf25bee-bda0-4eac-b7ea-5c926a3f5427","order_by":3,"name":"ShuMei Wang","email":"","orcid":"","institution":"Department of Neonatology, Faculty of Pediatrics, Seventh Medical Center of PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"ShuMei","middleName":"","lastName":"Wang","suffix":""},{"id":591706352,"identity":"1db67724-d7ac-4558-bca9-69f226941509","order_by":4,"name":"Feng Wang","email":"","orcid":"","institution":"Department of Neonatology, Faculty of Pediatrics, Seventh Medical Center of PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Feng","middleName":"","lastName":"Wang","suffix":""},{"id":591706353,"identity":"46d67da3-6c9b-4500-8f1e-32b713872ba0","order_by":5,"name":"ZhiChun Feng","email":"","orcid":"","institution":"Department of Neonatology, Faculty of Pediatrics, Seventh Medical Center of PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"ZhiChun","middleName":"","lastName":"Feng","suffix":""},{"id":591706354,"identity":"fe38a686-04e5-4884-bae4-3d75ff407fd6","order_by":6,"name":"QiuPing Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYDACCYY0EMXDwMDc+CChooYELTwMjM0GD84cI0oLGwPEGsY2yYctzIR1yM9uePbgw587MvbsB9sqEhvYGPjbuxPwamGccyDdcGbbMx4ensS2G4k7ZBgkzpzdgFcLs0RCmjRvw2GgX0BazrAxGEjk4tfCBtLC8weohf9hW0FiGzNhLTxgLWxALRKJbQxEaZEAapEE++XGw2aJhDPHeAj6RX5GTpoEMMTs2fuTD378UVEjx9/ei18L0GkJQOIAgktAOQiwH0DRMgpGwSgYBaMAAwAAl4NH1dOfHbkAAAAASUVORK5CYII=","orcid":"","institution":"Department of Neonatology, Faculty of Pediatrics, Seventh Medical Center of PLA General Hospital","correspondingAuthor":true,"prefix":"","firstName":"QiuPing","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2026-02-10 09:38:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8839125/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8839125/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103165307,"identity":"1b5ce3e4-2c47-4367-9518-7bf51c22e1c9","added_by":"auto","created_at":"2026-02-22 12:26:50","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":79985,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of case selection\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8839125/v1/443819d1b1e7af8e8a17125d.jpeg"},{"id":103504390,"identity":"a47ef020-60e5-453b-9095-d4ddc991234b","added_by":"auto","created_at":"2026-02-26 13:19:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":942241,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8839125/v1/c02a7d8c-a693-45ee-b129-47d6e215afbc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Ureaplasma urealyticum and Clinical Outcomes in Extremely Premature Infants: A Single-Center Retrospective Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003e \u003cem\u003eUreaplasma\u003c/em\u003e species are common colonizers and opportunistic pathogens in the neonatal period\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. A large-scale epidemiological survey in China revealed that among hospitalized newborns with detected \u003cem\u003eUreaplasma urealyticum\u003c/em\u003e (Uu) positivity, up to 93.99% were within the neonatal age range, indicating that Uu represents a clinically significant microorganism in this vulnerable population\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. This finding is particularly pronounced in preterm infants: the rate of Uu positivity in very preterm infants born before 26 weeks of gestation can reach approximately 65%\u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe association between Uu and adverse outcomes in preterm infants-especially bronchopulmonary dysplasia (BPD)-has long been a major focus in neonatology\u003csup\u003e\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Numerous retrospective studies have reported a significantly higher incidence of BPD in Uu-positive preterm infants compared with Uu-negative controls\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. The underlying pathological mechanism is believed to involve a persistent pulmonary inflammatory response induced by Uu, which plays a central role in the development and progression of BPD\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. However, existing clinical evidence remains contradictory: multiple studies have reported inconsistent findings regarding the association between Uu and BPD risk\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. This heterogeneity may arise from variations across studies in baseline infant characteristics such as gestational age and birth weight, differences in diagnostic criteria for BPD, and insufficient differentiation in the timing of Uu detection, colonization sites, and strain virulence. Furthermore, most prior studies have analyzed preterm infants as a broad, heterogeneous group, failing to adequately delineate the independent impact of Uu in the specific subpopulation of extremely preterm infants, who exhibit particularly intense inflammatory responses and extreme organ immaturity\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Previous research has shown that in cases of preterm premature rupture of membranes (PPROM) with Uu amniotic infection, an earlier gestational age at membrane rupture is associated with a stronger intra-amniotic inflammatory response\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. This suggests that in extremely preterm infants, Uu colonization or infection may trigger an amplified inflammatory cascade, thereby exacerbating injury to developing organ systems, including the lungs.\u003c/p\u003e \u003cp\u003eGiven the high prevalence of Uu in extremely preterm infants, its potential to intensify inflammatory states, and the compounded risk resulting from the inherent vulnerability of this population, clarifying the independent effect of Uu positivity on comprehensive clinical outcomes-such as BPD severity, other preterm-related complications, and mortality-is crucial for improving clinical management and prognosis. Nevertheless, high-quality studies systematically examining the relationship between Uu colonization status and multidimensional clinical outcomes in extremely preterm infants remain scarce.\u003c/p\u003e \u003cp\u003e Therefore, this study aims to conduct a retrospective cohort analysis, rigorously controlling for key confounders such as gestational age and birth weight, to investigate whether Uu positivity is associated with short-term major clinical outcomes among extremely preterm infants treated in neonatal intensive care units in China. Outcomes of interest include BPD, sepsis, retinopathy of prematurity, in-hospital mortality, and others. This work intends to provide an evidence-based foundation for refined risk stratification and optimized timing of interventions in this high-risk population.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Population\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study included infants admitted to a tertiary neonatal intensive care unit (NICU) in Northern China (January 2019-June 2023) with GA\u0026thinsp;\u0026lt;\u0026thinsp;28 weeks, intubation within 6 hours of birth, and nasopharyngeal Uu culture within 2 hours of NICU admission. Uu culture was performed semiquantitatively using a mycoplasma isolation kit (Zhuhai DL Biotechnology). The study adhered to the Declaration of Helsinki and was approved by the institutional ethics board. Waiver of informed consent was granted per national regulations for retrospective studies.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was BPD, defined as oxygen requirement at 36 weeks\u0026rsquo; postmenstrual age\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Secondary outcomes included mortality, palliative care, ROP, durations of invasive/non-invasive ventilation, oxygen therapy, total respiratory support, and hospitalization.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe sample size was estimated based on a previous study \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e, in which the BPD incidence was approximately 78% in very low birth weight infants with maternal Ureaplasma colonization, compared to 43% in those without colonization. With 80% power and α\u0026thinsp;=\u0026thinsp;0.05, a sample size of \u0026gt;\u0026thinsp;25 infants per group was sufficient to detect significant differences.\u003c/p\u003e \u003cp\u003eContinuous variables were summarized by mean (range) or median (IQR), and categorical variables were described using count (percentage). Comparison among each group were done by Chi-square test, Fisher\u0026rsquo;s exact test, Mann-Whitney U test or independent t test. Relationships between variables and duration of treatment were analyzed by fitting linear regression models with 95% CI; model significance was evaluated by analysis of variance. All analyses were conducted using SPSS (Version 26).\u003c/p\u003e \u003cp\u003eVariates with a P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.1 were included in the multivariate logistic analysis. Multivariate analysis was performed by binary logistic regression and odds ratios (OR) and 95% confidence intervals (CI) were calculated. Statistical significance was accepted at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003e1.Study Population\u003c/b\u003e \u003c/p\u003e \u003cp\u003eDuring the study period, 292 preterm infants were admitted to the NICU within 72 hours of birth. Among these, 91 infants (31.2%) underwent Uu pharyngeal swab culture. Twelve infants were excluded due to gestational age (GA)\u0026thinsp;\u0026ge;\u0026thinsp;28 weeks, and 9 were excluded for incomplete data. A total of 70 infants were included in the final analysis, with Uu-positive (n\u0026thinsp;=\u0026thinsp;34, 48.57%) and Uu-negative (n\u0026thinsp;=\u0026thinsp;36, 51.43%) groups defined based on culture results (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Of these, 65.71% (46/70) developed BPD. The baseline clinical characteristics of the cohort are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003e2. Baseline Characteristics\u003c/b\u003e \u003c/p\u003e \u003cp\u003eNo significant differences were observed between the Uu-positive and control groups in gestational age (weeks, GA), birth weight, sex, singleton status, in vitro fertilization (IVF) rates, antenatal steroid/antibiotic use, macrolide prophylaxis, preterm premature rupture of membranes (PPROM), histologic chorioamnionitis, maternal age, 6-hour postnatal complete blood count (white blood cells, platelets, hemoglobin), Apgar scores (1- and 5-minute), or surfactant administration (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, the Uu-positive group had a significantly higher proportion of vaginally delivered infants (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics stratified by Ureaplasma Colonization status\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUreaplasma\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age (weeks), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26.03 (23.14, 27.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26.50 (23.00, 27.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight (g), mean (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e880.44 (570.00, 1290.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e950.00 (600.00, 1260.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.115\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (64.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24 (66.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.863\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingleton, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (67.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (61.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.568\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIn vitro fertilization (IVF) offspring, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (52.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19 (52.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.989\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntenatal steroids, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32 (94.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (97.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.609\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntenatal antibiotics, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (47.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21 (58.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntenatal macrolides, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (5.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.609\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePPROM\u0026thinsp;\u0026gt;\u0026thinsp;12 h, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (41.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (38.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.839\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistologic chorioamnionitis,n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28 (82.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28 (77.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.632\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaginal delivery, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31 (91.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (61.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age (median (IQR))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32.50 (27.00-35.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33.00 (29.25\u0026ndash;36.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.617\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukocyte count, \u0026times;109/l(Median (IQR))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19.05 (8.28\u0026ndash;35.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.18 (8.16\u0026ndash;24.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.398\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eplatelet count, (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e206.00\u0026thinsp;\u0026plusmn;\u0026thinsp;63.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e239.00\u0026thinsp;\u0026plusmn;\u0026thinsp;66.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHgb count, (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e147.71\u0026thinsp;\u0026plusmn;\u0026thinsp;22.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e152.74\u0026thinsp;\u0026plusmn;\u0026thinsp;24.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.412\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 min Apgar Score, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.50 (5.75-8.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8.00 (6.00\u0026ndash;8.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.314\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5 min Apgar Score, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.00 (7.75-9.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.00 (8.00\u0026ndash;10.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.382\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurfactant (any dose), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32 (94.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34 (94.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003ePROM Prelabour rupture of the membrane\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\u003cp\u003e\u003cstrong\u003e3. Secondary Outcomes\u003c/strong\u003e\u003c/p\u003e \u003cp\u003e3.As shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the two groups did not differ significantly in: Duration of hospitalization, clinically significant patent ductus arteriosus (PDA, requiring medical/surgical intervention), IVH, PVL, NEC, ROP, EUGR, Late-onset sepsis, meningitis, Death prior to discharge, Deafness or suspected deafness, persistent pulmonary arterial hypertension(PPHN), fungal infections, Using NO, Duration of peripheral venous nutrition, or using of vasoactive drugs (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePrimary and secondary outcomes by colonization status\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUreaplasma\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePositive group\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;34)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e(n\u0026thinsp;=\u0026thinsp;36)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of hospitalization, days, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112.00 (90.00-129.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94.00 (84.00-112.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.076\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePDA requiring treatment (drug), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (41.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.459\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePDA requiring treatment (ligation), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (5.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (55.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVH\u0026thinsp;\u0026ge;\u0026thinsp;grade 3, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (44.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (30.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.241\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePVL\u0026thinsp;\u0026ge;\u0026thinsp;stage 2, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (8.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (11.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNEC\u0026thinsp;\u0026ge;\u0026thinsp;stage 2, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (14.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (8.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.472\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eROP\u0026thinsp;\u0026ge;\u0026thinsp;stage 3, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (20.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (41.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.069\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEUGR, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (20.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (19.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.905\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLate onset sepsis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (55.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (41.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.234\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeningitis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (20.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (16.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.673\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath prior to discharge, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (5.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (5.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeafness or suspected deafness, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (8.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (8.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePPHN, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (73.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (63.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.462\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003efungal infection, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (8.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.114\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUsing NO, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (17.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (13.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.703\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of peripheral venous nutrition, days, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.70\u0026thinsp;\u0026plusmn;\u0026thinsp;22.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.89\u0026thinsp;\u0026plusmn;\u0026thinsp;14.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.293\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eusing of vasoactive drugs(\u0026le;7 days), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (44.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (25.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.105\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eROP Retinopathy of prematurity, BPD Bronchopulmonary dysplasia, IVH Intraventricular hemorrhage, NEC necrotizing enterocolitis, EUGR extrauterine growth restriction, PVL Periventricular leukomalacia.\u003c/p\u003e \u003cp\u003e \u003cb\u003e4. Respiratory Outcomes\u003c/b\u003e \u003c/p\u003e \u003cp\u003eComparative analysis of respiratory outcomes revealed that the Uu-positive group required significantly longer invasive ventilation (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002). No differences were observed in BPD severity grades, duration of oxygen therapy, non-invasive ventilation, total respiratory support, rates or duration of dexamethasone treatment (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBPD and respiratory support stratified by Ureaplasma colonization status\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eBPD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUreaplasma\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBPD, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24 (70.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (61.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.404\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBPD(Grade\u0026thinsp;\u0026ge;\u0026thinsp;2), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (47.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (27.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.095\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBPD(Grade\u0026gt;2), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (14.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of invasive ventilation, days, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32.00 (12.50\u0026ndash;41.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.00 (5.25\u0026ndash;24.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of non-invasive ventilation, days, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e42.00 (31.00-54.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40.00 (23.00-44.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.242\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration supplemental oxygen, days, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.00 (3.75\u0026ndash;18.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.00 (6.25-28.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.129\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of total respiratory support, days, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80.00 (63.75\u0026ndash;105.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e69.00 (55.75\u0026ndash;86.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDexamethasone, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (47.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (36.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.353\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of Dexamethasone, days, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.00 (0.00\u0026ndash;10.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.00 (0.00-9.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.382\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003e5. Multivariate Analysis for BPD\u003c/b\u003e \u003c/p\u003e \u003cp\u003eGiven BPD's multifactorial etiology, we evaluated whether Uu colonization independently contributed to BPD. Variables with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in univariate analysis (GA, sex, PDA treatment) were included in the logistic regression model. Stepwise regression identified only GA (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.026) and male sex (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009) as independent BPD risk factors. Uu colonization showed no significant association (this factor did not meet the entry criteria for regression analysis) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate logistic analysis of factors associated with BPD\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariates\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBPD(n\u0026thinsp;=\u0026thinsp;46)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eno BPD(n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdjusted OR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age (weeks), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26.14 (25.00\u0026ndash;27.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27.07 (26.14\u0026ndash;27.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.533 (0.307, 0.926)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male), male, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34 (73.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.032 (1.558, 23.353)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePDA requiring treatment (drug and ligation), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26 (56.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (37.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.283 (0.078, 1.026)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective study found that: 1) The positive rate of early postnatal Uu culture via pharyngeal swab was significantly higher in extremely preterm infants delivered vaginally compared to those delivered by cesarean section; 2) After adjusting for confounders, early postnatal Uu positivity was not an independent risk factor for BPD in extremely preterm infants, nor did it significantly increase the risk of other severe complications (such as ROP, sepsis) or total hospital stay; 3) Uu positivity was independently associated with a longer duration of invasive mechanical ventilation.\u003c/p\u003e \u003cp\u003eThe higher rate of Uu positivity in vaginally delivered infants in this study aligns with the established understanding that Uu is primarily transmitted through vertical mother-to-child transmission\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Epidemiological surveys indicate that the vertical transmission rate from Uu-infected mothers to their neonates can range from 18% to 88%\u003csup\u003e1,24\u003c/sup\u003e. Uu detection is significantly associated with vaginal delivery and maternal genital tract colonization, supporting the notion that exposure during delivery is the primary route of neonatal acquisition\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.This finding has clinical implications: given the association between maternal genital Uu infection and adverse pregnancy outcomes such as chorioamnionitis, preterm premature rupture of membranes, and preterm birth\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e, future research could explore the potential value of perinatal Uu screening in high-risk pregnant populations.\u003c/p\u003e \u003cp\u003eNumerous studies have reported an epidemiological link between Uu and BPD in preterm infants\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. This study also observed that Uu-positive infants required longer invasive respiratory support\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e, suggesting that Uu colonization may exacerbate airway inflammation and injury. This is consistent with the previous view that Uu can induce pulmonary inflammatory responses and increase oxygen dependency\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Autopsy studies have also found more pronounced pulmonary fibrosis and inflammatory cell infiltration in very low birth weight infants with Uu infection\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. However, this apparent association often diminishes or disappears after controlling for confounding factors. For example, Chen et al. found that after adjusting for variables such as gestational age, the association between Uu-related pneumonia and BPD lost statistical significance\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. A Polish study similarly suggested that Uu exposure only increased the risk of BPD when coexisting with prolonged mechanical ventilation\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. The multiple regression analysis in this study led to a similar conclusion: gestational age at birth and sex were independent risk factors for BPD, whereas postnatal Uu positivity via pharyngeal swab was not an independent predictor.This collective evidence underscores the complexity of the Uu-BPD relationship: their association may be confounded or modified by various factors including gestational age, duration of mechanical ventilation, definition of infection (colonization vs. invasive infection), and strain virulence.\u003c/p\u003e \u003cp\u003eGiven the association between Uu colonization and prolonged ventilation, eradicating Uu might theoretically improve outcomes. However, recent high-quality randomized controlled trials (such as the AZTEC trial) have shown that postnatal prophylactic use of azithromycin neither reduces the incidence of BPD nor improves long-term neurodevelopmental outcomes\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. These negative results compel a reassessment of the critical time window for Uu-induced lung injury.\u003c/p\u003e \u003cp\u003eGrowing evidence points to the pivotal role of prenatal intrauterine exposure\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e.Studies indicate that intra-amniotic Uu infection (but not infection with other microorganisms or inflammation alone) is independently associated with an increased risk of BPD\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. Furthermore, obstetric research suggests that the benefit of azithromycin in improving outcomes for extremely preterm infants may be mediated primarily by influencing the intrauterine infection milieu rather than treating the neonate\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e.This hypothesis is supported by pathological findings: in analyses of causes of death in preterm infants, Uu is the most frequently detected microorganism in placental/membrane tissues, yet its detection rate in fetal/neonatal parenchymal tissues is much lower\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. This implies that Uu invasion of the fetal membranes, triggering an intrauterine inflammatory response, may be the primary mechanism leading to altered fetal lung development programming and increased BPD risk, whereas postnatal respiratory tract colonization might merely be a continuation or a secondary marker of this process.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, as a retrospective analysis, data on maternal genital tract Uu colonization status and placental/amniotic fluid pathology were unavailable for all infants, making it difficult to distinguish between intrauterine infection and postnatal colonization. Second, during the study period, pharyngeal swab culture was routinely performed only on intubated infants, potentially introducing selection bias. Finally, the relatively small sample size may have limited the power to detect subtle effect differences.\u003c/p\u003e \u003cp\u003eIn summary, this study found that vaginal delivery significantly increases the risk of postnatal respiratory Uu colonization in extremely preterm infants, and that Uu colonization is independently associated with prolonged invasive ventilation.However, it did not confirm Uu colonization as an independent risk factor for BPD. Integrating recent clinical trial data and mechanistic research, we hypothesize that the inflammatory environment induced by prenatal intrauterine Uu exposure, rather than mere postnatal colonization, may be the key driver in the pathogenesis of BPD. Future research should employ prospective designs, combine assays of maternal genital tract, placental, amniotic fluid, and serial neonatal samples, and incorporate microbial virulence analysis to more precisely elucidate the exact role of Uu in preterm lung development and to provide a basis for targeted prenatal intervention strategies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBPD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBronchopulmonary dysplasia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEUGR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eextrauterine growth restriction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003egestational age\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIVF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003evitro fertilization\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIVH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntraventricular hemorrhage\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNEC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enecrotizing enterocolitis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eneonatal intensive care unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePDA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epatent ductus arteriosus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePPHN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epersistent pulmonary arterial hypertension\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePPROM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epreterm premature rupture of membranes\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePVL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePeriventricular leukomalacia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eROP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRetinopathy of prematurity\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUu\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUreaplasma urealyticum\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eClinical trial number: not applicable\u003c/strong\u003e\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eThe study adhered to the Declaration of Helsinki and was approved by the institutional ethics board. The retrospective study was approved by the Ethics Committee of the Seventh Medical Center of the Chinese PLA General Hospital. Waiver of informed consent was granted per national regulations for retrospective studies.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis work was supported by the National Key Research and Development Program of China (2021YFC2701701).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYM and ZF designed the research, XH analyzed the data, YM and QL wrote the manuscript; HL, SW and ZC analyzed and interpreted the data; QL and ZF designed the research, analyzed the data, and corrected the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNo.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eVenturelli, N., Zeis, A., De Beritto, T. \u0026amp; Hageman, J. 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Dis.\u003c/em\u003e \u003cb\u003e76\u003c/b\u003e (3), e1004\u0026ndash;e1011. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/cid/ciac747\u003c/span\u003e\u003cspan address=\"10.1093/cid/ciac747\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2023).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"extremely preterm infants, Ureaplasma urealyticum, bronchopulmonary dysplasia","lastPublishedDoi":"10.21203/rs.3.rs-8839125/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8839125/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003e \u003cem\u003eUreaplasma urealyticum\u003c/em\u003e (Uu) colonization is associated with an increased risk of preterm birth. However, whether postnatal Uu colonization in extremely preterm infants affects clinical outcomes\u0026mdash;particularly bronchopulmonary dysplasia (BPD)-remains inconsistent in current evidence, with limited domestic research available.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included extremely preterm infants admitted to the neonatal intensive care unit between January 2019 and June 2023, who underwent Uu culture via pharyngeal swab within 6 hours after birth (within 2 hours after admission). Infants were divided into Uu-positive and Uu-negative groups based on culture results. Perinatal data and clinical outcomes were collected, and multiple regression analysis was performed to examine the independent association between Uu positivity and BPD, as well as other major outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 70 extremely preterm infants were included, of whom 46 (65.7%) required oxygen supplementation at a postmenstrual age of 36 weeks, meeting the diagnostic criteria for BPD. The proportion of infants delivered vaginally was significantly higher in the Uu-positive group than in the Uu-negative group (91.18% vs. 61.11%, P\u0026thinsp;=\u0026thinsp;0.003). The duration of invasive mechanical ventilation was longer in the Uu-positive group (P\u0026thinsp;=\u0026thinsp;0.002). Linear regression indicated that both gestational age at birth and Uu positivity significantly influenced the duration of invasive ventilation. However, after adjusting for confounders such as gestational age, birth weight, and mode of delivery in multiple regression analysis, postnatal Uu positivity via pharyngeal swab was not identified as an independent risk factor for BPD.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eVaginal delivery may increase the risk of postnatal Uu colonization in the respiratory tract of extremely preterm infants. Uu colonization is associated with a longer duration of invasive mechanical ventilation, but this study did not confirm it as an independent risk factor for BPD. Future studies with larger sample sizes and prospective designs are needed to further clarify the role of Uu in lung development in extremely preterm infants.\u003c/p\u003e","manuscriptTitle":"Ureaplasma urealyticum and Clinical Outcomes in Extremely Premature Infants: A Single-Center Retrospective Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-22 12:26:43","doi":"10.21203/rs.3.rs-8839125/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-07T10:47:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T22:36:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"320614023493288846745960727195706779467","date":"2026-04-28T22:35:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-06T12:50:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"43410541962548211945622469510030046056","date":"2026-04-02T08:18:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"288803251308421630436761428115232815466","date":"2026-03-31T23:35:04+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-13T13:47:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-13T11:23:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-11T12:28:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-11T12:27:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-02-10T08:53:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"503df15e-4b72-4331-a682-8f3b7dd443ba","owner":[],"postedDate":"February 22nd, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-07T10:47:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T22:36:07+00:00","index":131,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[{"id":62962820,"name":"Health sciences/Diseases"},{"id":62962821,"name":"Health sciences/Health care"},{"id":62962822,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-05-07T10:55:53+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-22 12:26:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8839125","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8839125","identity":"rs-8839125","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}