Impact of Evidence-Based Practice Bundles on Clinical Outcomes in Very Preterm Infants: A Multicenter Retrospective Study

Impact of Evidence-Based Practice Bundles on Clinical Outcomes in Very Preterm Infants: A Multicenter Retrospective Study | 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 Research Article Impact of Evidence-Based Practice Bundles on Clinical Outcomes in Very Preterm Infants: A Multicenter Retrospective Study Jing Feng, Xin Guo, Rui Li, Haiping Cheng, Yuanyuan LI, Kanghua Zhou, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7249012/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Although evidence-based practices (EBPs) can improve outcomes in very preterm infants (VPIs), real-world implementation rates and evidence regarding their synergistic effects remain limited. This study, which is based on the Shenzhen Neonatal Data Network (SNDN), evaluated the current implementation status of EBPs and the impact of their synergistic effects on clinical outcomes. Methods We conducted a retrospective study on 536 VPIs with a gestational age <32 weeks in 2024. These infants were categorized into asurvival without major morbidity (SWMM) group and an adverse outcome group (severe complications/death), with differences in the implementation of evidence-based practices (EBPs) evaluated between the two groups. Using the "all-or-none" approach, we further assessed five core EBPs: delivery at an experienced perinatal center; complete course of antenatal corticosteroids (ACS); antenatal magnesium sulfate (MgSO₄); maintenance of normothermia (36.5°C--37.5°C) within one hour after birth; and caffeine therapy.Multivariate logistic regression analysis was employed to explore the associationsbetween EBP implementation and adverse outcomes. Results Bundle implementation of five EBPs significantly reduced adverse outcomes in VPIs (aOR=0.47, 95% CI: 0.25–0.90). Independent protective factors included delivery at RDS-experienced centers (aOR=0.18, 95% CI: 0.04–0.86); delayed cord clamping (DCC)/umbilical cord milking (UCM) (aOR=0.55, 95% CI: 0.31–0.96);and normothermia within the first hour after birth (aOR=0.58, 95% CI: 0.37–0.91). Only 19.2% of VPIs received all five EBPs. The lowestimplementation rates were reported for normothermia within the first hour after birth (49.4%) and DCC/UCM (23.3%). Conclusions Bundled implementation of EBPs significantly improves clinical outcomes in VPIs. However, suboptimal adherence—particularly for normothermia within the first hour after birth and DCC/UCM—necessitates targeted quality improvement initiatives. We can enhance quality and improve SWMM in VPIs by systematically improving the implementation rates of EBPs. Evidence-based practices Very preterm infants Outcome Mortality Survival without major morbidity Figures Figure 1 Figure 2 Introduction Preterm birth is the leading cause of neonatal mortality and is associated with long-term physical, neurodevelopmental, and socioeconomic effects, especially for very preterm infants (VPIs) [1]. Although improvements in neonatal care have increased survival without major morbidity (SWMM) among VPIs[2, 3], the burdens of neonatal mortality and severe complications attributable to VPIs remain substantial[4]. The implementation of evidence-based practices (EBPs) can reduce preterm infant mortality, effectively prevent severe complications, and improve clinical outcomes[5-7]. Although evidence-based guidelines have been established in various countries, significant variations exist in the implementation of these practices. Systematic research concerning the actual implementation rates in real-world clinical settings and the cumulative impact on preterm infant outcomes is lacking. This study retrospectively evaluated the implementation of EBPs for VPIs with a gestational age (GA) <32 weeks in the SNDN on the basis of the 2022 European Consensus Guidelines for Respiratory Distress Syndrome (RDS) management[8]. The cumulative effects of five key EBPs on clinical outcomes in this population were further analysed, aiming to provide evidence for standardized clinical practice. Patients and methods Study population Inclusion criteria: Data for this multicenter study were obtained from the SNDN databases on VPIs with a GA <32 weeks who were admitted to the neonatal intensive care unit (NICU) between 1st January 2024 and 31st December 2024. The exclusion criteria were as follows: (1) treatment withdrawal for nonmedical factors within 24 hours after birth (n=11); (2) major congenital anomalies that may affect the outcome (n=4); (3) major data gaps (n=6); (4) the outcome after transfer treatment is unknown (n=50); and (5) patients from centers with enrollment <20 (n=112) (Fig. 1). Definition of EBPs: using an all -or-none approach We used an all-or-none approach to study the use of EBPs. In contrast with an item-by-item assessment of performance or the creation of a composite measure, this approach considers whether all measures have been provided to each eligible patient[9]. A restrained set of indicators is selected that should measure performance on the specified elements of good practice and be related to the desired outcomes. Our study evaluated adherence to the 10 EBPs outlined in the protocol of the 2022 European respiratory distress syndrome guidelines, from which we identified five with a high level of evidence related to neonatal mortality and morbidity that could be measured reliably via information from medical records. Some EBPs included in the protocol were excluded because of inconsistent implementation by all hospitals, such as deferring cord clamping (DCC), umbilical cord milking (UCM), and the use of a T-piece resuscitator. The selected indicators were (1) delivery in a maternity unit with experience in the management of RDS; (2) a complete course of antenatal corticosteroids (ACSs) before delivery; (3) antenatal magnesium sulfate (MgSO 4 ); (4) normothermia (36.5°C--37.5°C) within the first hour after birth; and (5) caffeine therapy. Definition of outcomes The primary outcome was a composite of severe complications and/or death. Severe complications were defined as the presence of any of the following: ≥grade 3 intraventricular hemorrhage[10] and/or periventricular leukomalacia (IVH/PVL)[11], moderate-to-severe bronchopulmonary dysplasia (BPD) (defined by the NICHD 2001 criteria)[12], grade 3 necrotizing enterocolitis (NEC)[13], and ≥grade 3 retinopathy of prematurity (ROP) and/or surgical treatment[14]. Death was defined as either in-hospital mortality or death within 24 hours after treatment withdrawal. SWMM is defined as survival to 36 weeks postmenstrual age or hospital discharge (whichever comes first) without grade ≥3 IVH/PVL, Bell's stage ≥3 NEC, moderate/severe BPD, or severe ROP. Covariables We identified clinical and healthcare factors likely to influence the probability of receiving evidence-based practices and outcomes. These factors included gestational age, sex, birth weight, small for gestational age, type of delivery, multiple pregnancy, maternal age, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), assisted reproductive technology (ART), and 1-minute and 5-minute Apgar scores. Statistical analyses All continuous variables were subjected to normality assessment via the Shapiro‒Wilk test. Nonnormally distributed continuous variables are summarized as medians (interquartile ranges, IQRs) and were compared with the Mann‒Whitney U test. Categorical variables are described as frequencies and percentages and were analysed by the chi-square test. Missing data (<5%) were handled by complete-case analysis. The impact of EBP measures on adverse outcomes was assessed via logistic regression analysis. A multivariate logistic regression model was used to adjust for potential confounding factors, including gestational age, sex, birth weight, delivery mode, conception method, and a 1-minute Apgar score ≤7. Adjusted results are reported with adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs). All the statistical analyses were conducted via SPSS Statistics 27.0, with a p value <0.05 considered statistically significant. Results Study population characteristics A total of 536 VPIs with a GA < 32 weeks were included, with an overall median GA of 30.0 weeks and a median birth weight (BW) of 1245 g. These infants were stratified into SWMM (n = 380) and severe complication/death (n = 156) groups. Significant intergroup differences were observed: the severe complications/death group had lower GA (median 27.9 vs. 30.4 weeks, P < 0.001) and BW (median 960 g vs. 1360 g, P < 0.001) values. Higher rates of assisted reproductive technology (26.3% vs. 18.0%, P = 0.031), lower cesarean section rates (59.6% vs. 73.7%, P = 0.001), and a higher proportion of patients with a 1-minute Apgar score ≤ 7 (30.1% vs. 13.7%, P 0.05) (Table 1 ). Table 1 Baseline characteristics and outcomes Variables, n(%) SWMM (n = 380) Severe complications/death(n = 156) Total(n = 536) χ ༒ /Z P value Gestational Age(weeks)median (IQR) 30.4(29.1,31.3) 27.9(26.1,29.7) 30(28.1,31) -10.574 <0.001* Sex, Male 212(55.8) 101(64.7) 313(58.4) 3.65 0.056 Birth Weight(g), median(IQR) 1360(1130,1520) 960(800,1200) 1245(990,1490) -10.294 <0.001* small for gestational age 17(4.5) 12(7.7) 29(5.4) 2.239 0.135 ART 68(18) 41(26.3) 109(20.4) 4.674 0.031* multiple pregnancy 105(27.7) 46(29.5) 151(28.2) 0.641 0.726 maternal age(y), median(IQR) 32(29,35) 31(29,35) 31(29,35) −0.795 0.426 Cesarean section 278(73.7) 93(59.6) 371(69.6) 10.405 0.001* GDM 127(33.4) 39(25.2) 166(31) 3.51 0.061 HDP 75(19.8) 33(21.3) 108(20.3) 0.143 0.705 1-minute Apgar score < 7 52(13.7) 47(30.1) 99(18.5) 19.86 <0.001* 5-minute Apgar score < 7 11(2.9) 9(5.8) 20(3.7) 6.275 0.111 Abbreviations: SWMM, survival without major morbidity; GDM, gestational diabetes mellitus; HDP, hypertensive disorders of pregnancy; ART, assisted reproductive technology. * p < 0.05 indicates statistical significance. Evidence-Based Practices (EBPs) Adherence Adherence to EBPs was significantly different between the two groups. The severe complications/death group exhibited significantly lower adherence to key EBPs (Table 2 ): complete ACS (44.9% vs. 55.8%, P = 0.021). DCC/UCM (4.9% vs. 18.5%, P = 0.020); normothermia (36.5°C-37.5°C) within the first hour after birth (36.5% vs. 54.7%, P < 0.001); caffeine administration rate within 48 hours after birth (88.3% vs. 94.3%, P = 0.024); and enteral nutrition within 24 h (42.9% vs. 67.0%, P < 0.001). T-piece resuscitator use was greater in the severe complications/death group (75.8% vs. 65.8%, P = 0.008), likely reflecting greater illness severity. Table 2 Outcome Comparisons by Exposure to Specific Evidence-Based Practices (EBPs) EBPs SWMM(n = 380) Severe complications/death(n = 156) Total (n = 536) Χ 2 /Z P value ACS 337(89.6) 141(91.6) 478(90.2) 0.46 0.497 Complete course of ACS 212(55.8) 70(44.9) 282(52.6) 5.288 0.021* Magnesium sulfate 282(74.2) 107(68.6) 389(72.6) 1.755 0.185 Inborn delivery 376(98.9) 150(96.2) 526(98.1) - 0.04* DCC/UCM 99(18.5) 26(4.9) 125(23.3) 5.449 0.02* T-piece use in the delivery room 235(65.8) 113(75.8) 348(68.8) 15.027 < 0.001* Normothermia 208(54.7) 57(36.5) 265(49.4) 14.653 < 0.001* PS 165(43.4) 119(76.3) 284(53) 47.942 < 0.001* Initial dose of PS 173.9(142.9,200) 179.8(142.4,200) 176.5(142.9,200) −1.287 0.198 Caffeine therepy 335(88.2) 137(87.8) 472(88.1) 0.012 0.913 Caffeine within 48 hours after birth 316(94.3) 121(88.3) 437(92.6) 5.111 0.024* Enteral feeding within 24 hours 238(67) 57(42.9) 295(60.5) 23.671 < 0.001* Abbreviations: ACS, antenatal corticosteroids; DCC, deferring cord clamping; UCM, umbilical cord milking; PS, pulmonary surfactant. * p < 0.05 indicates a statistically significant difference. Figure 2 shows the implementation of all or none of the five EBPs. Specifically, 52.6% (n = 282) received a complete course of ACS, 72.6% (n = 389) were administered antenatal MgSO 4 for fetal neuroprotection, 98.1% (n = 526) were delivered at tertiary perinatal centers with RDS management capabilities, 49.4% (n = 265) achieved normothermia (≥ 36.5°C) within the first hour after birth, and 88.1% (n = 472) received caffeine therapy. However, only 19.2% (n = 103) of the infants received all five EBPs concurrently (Fig. 2 ). As the GA increased from < 24 weeks to 30–31 + 6 weeks, we observed increasing implementation trends for key EBPs: normothermia maintenance (33.3% → 55.1%, P = 0.043) and overall bundle adherence (0% → 19.9%), although most EBPs showed no statistical significance (Table 4 ). Table 4 Logistic regression analyses examining the association of EBPs with severe complications/death Variables Crude OR(95%CI) P value Adjusted OR(95%CI) P value Complete course of ACS 0.65(0.44,0.94) 0.022 0.71(0.45,1.12) 0.139 Magnesium sulfate 0.76(0.50,1.14) 0.186 0.61(0.37,1.0) 0.051 Inborn delivery 0.27(0.07,0.96) 0.042 0.18(0.04,0.86) 0.032* DCC/UCM 0.57(0.35,0.92) 0.021 0.55(0.31,0.96) 0.034* Normothermia 0.48(0.32,0.70) < 0.001 0.58(0.37,0.91) 0.019* Caffeine therepy 0.97(0.55,1.72) 0.913 1.06(0.51,2.22) 0.88 All EBPs 0.39(0.22,0.69) 0.001 0.44(0.23,0.84) 0.013* Abbreviations: OR, odds ratio; CI, confidence interval. Adjusted for gestational age, sex, birth weight, mode of conception, type of delivery, and 1-min Apgar score. * p < 0.05 indicates a statistically significant difference. Impact of EBPs on Outcomes Multivariate regression analysis (adjusted for gestational age, sex, birth weight, conception method, delivery mode, and 1-minute Apgar score ≤ 7) revealed that three EBPs were significantly associated with a reduction in severe complications/deaths: delivery at centers with RDS management capabilities (aOR = 0.18, 95% CI: 0.04–0.86; P = 0.032). DCC/UCM (aOR = 0.55, 95% CI: 0.31–0.96, P = 0.034), and normothermia (36.5–37.5°C) within the first hour after birth (aOR = 0.58, 95% CI: 0.37–0.91, P = 0.019). Although a complete course of ACS, antenatal MgSO 4 , and caffeine therapy demonstrated no independent protective effects after adjustment (P > 0.05), concurrent implementation of all five EBPs significantly reduced adverse outcome risk (aOR = 0.44, 95% CI: 0.23–0.84, P = 0.013). Discussion The all-or-none assessment method enables effective evaluation of the implementation status and improvement opportunities for high-quality EBPs with extensive validation[ 5 , 15 – 17 ]. In this study, we applied the all-or-none approach to analyse the five EBPs. Our analysis demonstrated that VPIs receiving all EBPs presented a significantly reduced incidence of adverse outcomes (aOR = 0.44; 95% CI: 0.23–0.84; P = 0.013). These findings indicate that the comprehensive implementation of high-quality evidence-based guidelines improves preterm infant prognosis and reduces adverse event rates. However, only 19.2% received the complete bundle, indicating significant gaps in quality improvement—particularly for underperforming interventions such as normothermia within the first hour after birth (49.4%) and DCC/UCM (23.3%), which demonstrated critically low implementation rates in this study. The five EBPs bundled in our study have each been proven to improve the clinical outcomes of VPIs. For the first EBPs (inborn deliveries at centers with RDS management capabilities), many studies have shown that birth in a maternity unit, which is termed a level III hospital, is associated with better outcomes for VPIs[ 18 – 20 ]. All nine included hospitals were Level 3 facilities, where 98.1% of deliveries occurred. VPIs born at these hospitals demonstrated a significantly reduced incidence of adverse outcomes (aOR = 0.18; 95% CI: 0.04–0.86; P = 0.032). For the second practice (complete course of ACS), meta-analyses of observational studies have shown that ACS reduces the risk of perinatal death (RR = 0.85, 95% CI: 0.77–0.93) neonatal death (RR = 0.78, 95% CI: 0.70–0.87; RDS (RR = 0.71, 95% CI: 0.65–0.78)) and probably reduces the risk of IVH (RR = 0.58, 95% CI: 0.45–0.75). The administration rate for infants born at < 32 weeks ranges from 82–93% in developed countries [ 21 ]. In China, a large-scale survey reported an ACS utilization rate of 78.0%, with only 49.1% of these cases receiving a complete course [ 22 ]. Our study revealed higher rates: 90.2% for ACS administration and 52.6% for the complete course. These figures exceed China's national averages and approach those documented in developed countries. The dosage, treatment course completeness, and timing of ACS administration may all potentially impact outcomes in VPIs[ 23 – 26 ]. In our study, although the group receiving a complete course of ACS demonstrated a significantly lower incidence of adverse outcomes than the SWMM group did, the aOR was not significantly different. This may be attributed to our composite outcome incorporating multiple severe complications, which potentially weakened the association between ACS exposure and individual adverse outcomes. For third-EBPs (antenatal MgSO 4 ), substantial evidence confirms that antenatal MgSO 4 administration reduces the risk of cerebral palsy, although it has no significant association with overall infant mortality[ 27 , 28 ]. Although not associated with short-term clinical outcomes, MgSO₄ remains recommended as standard practice because of its established association with significantly reduced long-term neurodevelopmental sequelae such as cerebral palsy. Similarly, in our study, MgSO₄ was not significantly associated with short-term outcomes. However, when evaluated through the all-or-none composite assessment, it contributes to improved preterm infant outcomes when it is implemented collectively with other evidence-based interventions. MgSO 4 administration increased from 65.8% in 2017 to 85.5% in 2022 in England[ 29 ]. In our study, the administration rate of MgSO₄ was 72.6%, indicating the ongoing potential for improvement. Our fourth evidence-based practice targeted the maintenance of normothermia within the first hour after birth. A recent systematic review published in Pediatrics demonstrated that the mean hypothermia rate was 42% (range 14%-88%), and hypothermia was associated with increased mortality (aOR = 1.55, 95% CI: 1.29–1.87)[ 30 ]. In our study, maintaining normothermia within the first hour after birth similarly demonstrated a reduced likelihood of the composite outcome of severe adverse events or mortality in VPIs (aOR = 0.58; 95% CI: 0.37–0.91). However, the observed incidence rate of hypothermia (50.6%) remained higher than the benchmark rates, necessitating targeted improvement initiatives. For the fifth evidence-based practice (caffeine therapy), meta-analyses indicate that caffeine administration reduces the incidence of BPD [ 31 ] and decreases the risk of extubation failure [ 32 ]. However, the optimal timing for caffeine initiation remains debated [ 33 ]. Our study revealed that, compared with the SWMM group, the severe complications/death group had significantly lower caffeine administration rates within 48 hours after birth (88.3% vs. 94.3%; P = 0.024). As gestational age advances, the implementation rates of EBPs tend to increase (e.g., normothermia increased from 33.3–55.1%). However, all EBP coverage remained near zero for periviable infants (< 24 weeks) (Table 3 ). This cohort has an adverse outcome rate as high as 88.9%, indicating a gap compared with international benchmarks. A meta-analysis revealed substantial disparities in the survival rates of extremely immature infants at 22–25 weeks gestation across different economic settings[ 34 ], highlighting global inequities in perinatal health. Sustained research and collaborative efforts remain crucial to further improve global survival and long-term outcomes for infants with survival potential. Table 3 EBPs and outcomes by gestational age Variables ≤ 24 24–26 + 6 27–29 + 6 30–31 + 6 Χ 2 P value Complete course of ACS 3(33.3) 28(46.7) 97(50.8) 154(55.8) 3.54 0.313 Magnesium sulfate 5(55.6) 44(73.3) 144(75.4) 196(71.0) 2.554 0.456 Inborn delivery 9(100) 59(98.3) 186(97.4) 272(98.6) 1.318 0.773 DCC/UCM 0(0) 14(23.3) 46(24.1) 65(23.6) 2.583 0.473 Normothermia 3(33.3) 24(40) 86(45) 152(55.1) 8.006 0.043* Caffeine therepy 6(66.7) 51(85) 175(91.6) 240(87) 6.971 0.061 All EBPs 0(0) 9(15) 38(19.9) 56(20.3) 2.553 0.457 Severe complications/death 8(88.9) a 47(78.3) a 70(36.6) b 31(11.2) c 131.217 < 0.001* * p 20 VPI cases in the SNDN database. All nine sites were tertiary hospitals, limiting the generalizability of the conclusions to primary care settings. Second, the exclusion of transferred patients lost to follow-up may have introduced selection bias in the implementation rates. Third, the retrospective design resulted in a reliance on medical record completeness for certain EBPs. For example, DCC implementation rates may be artificially low because of potential underreporting. A. Rizzolo et al. demonstrated that DCC synergistically reduces neonatal mortality when combined with other EBPs[ 16 ]. A meta-analysis provided high-certainty evidence that DCC reduces death before discharge in preterm infants[ 35 ]. Similarly, our study revealed that DCC/UCM reduces adverse outcomes (aOR = 0.55; 95% CI: 0.31–0.96). However, its limited sample size precluded inclusion in the bundle analysis. Fourth, our study population was limited in terms of short-term outcomes up to hospital discharge, precluding analysis of long-term neurodevelopmental outcomes. In summary, we demonstrated that bundle implementation of EBPs significantly reduces adverse outcomes in VPIs. Adherence to these practices can serve as a metric for evaluating a healthcare facility's quality of care and provide actionable insights for quality improvement. Nevertheless, the overall implementation rate of EBPs remains suboptimal, highlighting persistent challenges in translating effective interventions into routine clinical practice. Barriers include gaps in clinicians' knowledge and attitudes, organizational obstacles within units, and limitations in facility resources. Substantial opportunities exist for quality enhancement—by systematically improving EBP implementation rates, we can ultimately increase SWMM in this vulnerable population. Conclusions Bundled implementation of EBPs significantly improves clinical outcomes in VPIs. However, suboptimal adherence—particularly for normothermia within the first hour after birth and DCC/UCM—necessitates targeted quality improvement initiatives. We can enhance quality and improve SWMM in VPIs by systematically improving the implementation rates of EBPs. Abbreviations VPIs Very Preterm Infants SWMM survival without major morbidity EBPs evidence-based practices SNDN Shenzhen Neonatal Data Network GA gestational age BW birth weight RDS respiratory distress syndrome DCC deferring cord clamping UCM umbilical cord milking ACS antenatal corticosteroids MgSO4 magnesium sulfate GDM gestational diabetes mellitus HDP hypertensive disorders of pregnancy ART assisted reproductive technology BPD Bronchopulmonary Dysplasia IVH Intraventricular Hemorrhage NEC Necrotizing Enterocolitis NICU Neonatal Intensive Care Unit PVL Periventricular Leukomalacia ROP Retinopathy of Prematurity Declarations Ethics approval and consent to participate This study was conducted in accordance with the International Conference on Good Clinical Practice standards and the Declaration of Helsinki. The study received approval from the Ethics Committee of Longgang District Maternity & Child Healthcare Hospital of Shenzhen City (approval number: LGFYKYXMLL-2025-42) and was recognized by the ethics committees of all the participating institutions. Informed consent was waived at each site because the use of deidentified patient data. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Acknowledgements The authors want to thank all the participants in this study. Author contributions JF conducted all the data analyses and was the primary contributor to the writing of the manuscript. CC, HT and XG contributed to the conception and design of this study. RL and ZY offered clinical insights for interpreting the results. HC, YL, KZ, DR, GD and XY contributed to the acquisition, analysis and interpretation of the data. All the authors reviewed the manuscript and gave permission to be published. Funding This research received no specific grant from any funding agency. Data availability The datasets used and/or analysed during this study are available from the corresponding author upon reasonable request. Additional contributions The data in this study were provided by nine member hospitals of the SNDN, with participating institutions listed in alphabetical order as follows: Longgang District Maternity & Child Healthcare Hospital of Shenzhen City,Peking University Shenzhen Hospital,Shenzhen People's Hospital,Shenzhen Baoan District Maternity and Child Healthcare Hospital,Shenzhen Longgang District Central Hospital,Shenzhen Longhua District People’s Hospital,Shenzhen Longhua Maternity and Child Healthcare Hospital,Shenzhen Luohu People's Hospital,The People’s Hospital of Baoan Shenzhen. References Chen C, Zhang JW, Xia HW, Zhang HX, Betran AP, Zhang L, et al. Preterm Birth in China Between 2015 and 2016. Am J Public Health. 2019;109(11):1597–604. 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Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2020;12(12):Cd004454. Zhao J, Feng Z, Dai Y, Zhang W, Jiang S, Wang Y, et al. Use of antenatal corticosteroids among infants with gestational age at 24 to 31 weeks in 57 neonatal intensive care units of China: a cross-sectional study. Chin Med J (Engl). 2023;136(7):822–9. Schmitz T, Doret-Dion M, Sentilhes L, Parant O, Claris O, Renesme L, et al. Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial. Lancet. 2022;400(10352):592–604. Blickstein I, Reichman B, Lusky A, Shinwell ES. Plurality-dependent risk of severe intraventricular hemorrhage among very low birth weight infants and antepartum corticosteroid treatment. Am J Obstet Gynecol. 2006;194(5):1329–33. Battarbee AN, Ros ST, Esplin MS, Biggio J, Bukowski R, Parry S, et al. Optimal timing of antenatal corticosteroid administration and preterm neonatal and early childhood outcomes. Am J Obstet Gynecol MFM. 2020;2(1):100077. Fuma K, Kotani T, Tsuda H, Oshiro M, Tano S, Ushida T, et al. Impact of antenatal corticosteroids-to-delivery interval on very preterm neonatal outcomes: a retrospective study in two tertiary centers in Japan. BMC Pregnancy Childbirth. 2024;24(1):607. Conde-Agudelo A, Romero R. Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks' gestation: a systematic review and metaanalysis. Am J Obstet Gynecol. 2009;200(6):595–609. Shepherd ES, Goldsmith S, Doyle LW, Middleton P, Marret S, Rouse DJ, et al. Magnesium Sulfate Before Preterm Birth for Neuroprotection: An Updated Cochrane Systematic Review. Obstet Gynecol. 2024;144(2):161–70. Edwards HB, Sillero-Rejon C, McLeod H, Hill EM, Opmeer BC, Peters C et al. Implementation of national guidelines on antenatal magnesium sulfate for neonatal neuroprotection: extended evaluation of the effectiveness and cost-effectiveness of the National PReCePT Programme in England. BMJ Qual Saf. 2025. Hogeveen M, Hooft L, Onland W. Hypothermia and Adverse Outcomes in Very Preterm Infants: A Systematic Review. Pediatrics. 2025;155(5). Kua KP, Lee SW. Systematic review and meta-analysis of clinical outcomes of early caffeine therapy in preterm neonates. Br J Clin Pharmacol. 2017;83(1):180–91. Ferguson KN, Roberts CT, Manley BJ, Davis PG. Interventions to Improve Rates of Successful Extubation in Preterm Infants: A Systematic Review and Meta-analysis. JAMA Pediatr. 2017;171(2):165–74. Nylander Vujovic S, Nava C, Johansson M, Bruschettini M. Confounding biases in studies on early- versus late-caffeine in preterm infants: a systematic review. Pediatr Res. 2020;88(3):357–64. Li YX, Hu YL, Huang X, Li J, Li X, Shi ZY, et al. Survival outcomes among periviable infants: a systematic review and meta-analysis comparing different income countries and time periods. Front Public Health. 2024;12:1454433. Seidler AL, Aberoumand M, Hunter KE, Barba A, Libesman S, Williams JG, et al. Deferred cord clamping, cord milking, and immediate cord clamping at preterm birth: a systematic review and individual participant data meta-analysis. Lancet. 2023;402(10418):2209–22. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-7249012","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":544133573,"identity":"ae57ad05-eacb-4995-8a52-d584d5431363","order_by":0,"name":"Jing Feng","email":"","orcid":"","institution":"Longgang District Maternity \u0026 Child Healthcare Hospital of Shenzhen C ity (Longgang Maternity and Child Institute of Shantou University Medical 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Technology","correspondingAuthor":false,"prefix":"","firstName":"Zhangbin","middleName":"","lastName":"Yu","suffix":""},{"id":544133583,"identity":"7e548cc7-10fa-4927-bda2-55b3e2546b84","order_by":10,"name":"Cheng Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBACfvnDBx98+FEjx9jffIA4LZIz2JINZ/YcM2aecSyBOC0GN3jMhDnYmBPbG3IMiHTZ7R4zZgYeNmPehjMfb7xhsJPTbSCgg3HOsbLHBRYycpLNvZst5zAkG5sdIKCFmSF5u/EMoC2GDWe3SfMwHEjcRkgLG0OCmTQP0C/7D+Q8I04Lj0QKREtjQw4bcVokeI5BAplxxjFjyzkGRPjF/ngzPCof3nhTYSdHUAualcRGDZIWUnWMglEwCkbBiAAAZPtFG1VxlmUAAAAASUVORK5CYII=","orcid":"","institution":"Longgang District Maternity \u0026 Child Healthcare Hospital of Shenzhen C ity (Longgang Maternity and Child Institute of Shantou University Medical 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11:58:56","extension":"html","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":123060,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7249012/v1/5e8d08dc87fe60475aba3dd1.html"},{"id":96285681,"identity":"70e28a13-c4d1-4336-b3ae-8389fedbf180","added_by":"auto","created_at":"2025-11-19 11:58:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":80355,"visible":true,"origin":"","legend":"\u003cp\u003ePatient enrollment flowchart\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-7249012/v1/d61b06742479cb5f693eec71.png"},{"id":96285688,"identity":"b6961d42-eef8-4b34-9316-ee212cd73615","added_by":"auto","created_at":"2025-11-19 11:58:56","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":45302,"visible":true,"origin":"","legend":"\u003cp\u003eAll-or-none adherence rate to EBPs\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-7249012/v1/3ba73378a965ed0e8eb4f75d.png"},{"id":99816930,"identity":"9edf3494-0257-4f44-9bc2-ba03093a68ca","added_by":"auto","created_at":"2026-01-08 14:48:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":931677,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7249012/v1/352c710b-c4bc-4a47-b73e-2a70201a51c8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Evidence-Based Practice Bundles on Clinical Outcomes in Very Preterm Infants: A Multicenter Retrospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePreterm birth is the leading cause of neonatal mortality and is associated with long-term physical, neurodevelopmental, and socioeconomic effects, especially for very preterm infants (VPIs) [1]. Although improvements in neonatal care have increased survival without major morbidity (SWMM) among VPIs[2, 3], the burdens of neonatal mortality and severe complications attributable to VPIs remain substantial[4].\u003c/p\u003e\n\u003cp\u003eThe implementation of evidence-based practices\u0026nbsp;(EBPs) can reduce preterm infant mortality, effectively prevent severe complications, and improve clinical outcomes[5-7]. Although evidence-based guidelines have been established in various countries,\u0026nbsp;significant variations exist in the implementation of these practices.\u0026nbsp;Systematic research concerning the actual implementation rates in real-world clinical settings and the cumulative impact on preterm infant outcomes is lacking.\u003c/p\u003e\n\u003cp skip=\"true\"\u003eThis study retrospectively evaluated the implementation of EBPs for VPIs with a gestational age (GA) \u0026lt;32 weeks in the SNDN on the basis of the 2022 European Consensus Guidelines for Respiratory Distress Syndrome (RDS) management[8]. The cumulative effects of five key EBPs on clinical outcomes in this population were further analysed, aiming to provide evidence for standardized clinical practice.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInclusion criteria: Data for this\u0026nbsp;multicenter study were obtained from the SNDN databases on VPIs with a GA \u0026lt;32 weeks who were admitted to the neonatal intensive care unit (NICU) between 1st January 2024 and 31st December 2024.\u003c/p\u003e\n\u003cp\u003eThe exclusion\u0026nbsp;criteria were as follows: (1) treatment withdrawal for\u0026nbsp;nonmedical\u0026nbsp;factors within 24 hours after birth (n=11); (2) major congenital anomalies that may affect the outcome (n=4); (3) major data gaps (n=6); (4)\u0026nbsp;the outcome after transfer treatment is unknown (n=50); and (5) patients\u0026nbsp;from centers with enrollment \u0026lt;20 (n=112) (Fig. 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinition of EBPs: using an all\u003c/strong\u003e\u003cstrong\u003e-or-none approach\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe used an all-or-none approach to study the use of EBPs. In contrast with an item-by-item assessment of performance or the creation of a composite measure, this approach considers whether all measures have been provided to each eligible patient[9].\u003c/p\u003e\n\u003cp skip=\"true\"\u003eA restrained set of indicators is selected that should measure performance on the specified elements of good practice and be related to the desired outcomes. Our study evaluated adherence to the 10 EBPs outlined in the protocol of the 2022 European respiratory distress syndrome guidelines, from which we identified five with a high level of evidence related to neonatal mortality and morbidity that could be measured reliably via information from medical records. Some EBPs included in the protocol were excluded because of inconsistent implementation by all hospitals, such as deferring cord clamping (DCC), umbilical cord milking (UCM), and the use of a T-piece resuscitator.\u003c/p\u003e\n\u003cp\u003eThe selected indicators were (1) delivery in a maternity unit with experience in the management of RDS; (2) a complete course of antenatal corticosteroids (ACSs) before delivery; (3) antenatal magnesium sulfate (MgSO\u003csub\u003e4\u003c/sub\u003e);\u0026nbsp;(4)\u0026nbsp;normothermia (36.5\u0026deg;C--37.5\u0026deg;C) within the first hour after birth; and (5) caffeine therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinition of outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was a composite of severe complications and/or death. Severe complications\u0026nbsp;were defined as the presence of any of the following:\u0026nbsp;\u0026ge;grade 3 intraventricular hemorrhage[10] and/or periventricular leukomalacia (IVH/PVL)[11], moderate-to-severe bronchopulmonary dysplasia (BPD)\u0026nbsp;(defined by the NICHD 2001 criteria)[12], grade 3 necrotizing enterocolitis (NEC)[13], and \u0026ge;grade 3 retinopathy of prematurity (ROP) and/or surgical treatment[14].\u0026nbsp;Death was defined as either in-hospital mortality or death within 24 hours after treatment withdrawal. SWMM is defined as survival to 36 weeks postmenstrual age or hospital discharge (whichever comes first) without grade \u0026ge;3 IVH/PVL, Bell\u0026apos;s stage \u0026ge;3 NEC, moderate/severe BPD, or severe ROP.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCovariables\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe identified clinical and healthcare factors likely to influence the probability of receiving evidence-based practices and outcomes. These factors included gestational age, sex, birth weight, small for gestational age, type of delivery, multiple pregnancy, maternal age, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), assisted reproductive technology (ART), and 1-minute and 5-minute Apgar scores.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll continuous variables were subjected to normality assessment via the Shapiro‒Wilk test. Nonnormally distributed continuous variables are summarized as medians (interquartile ranges, IQRs) and were compared with the Mann‒Whitney U test. Categorical variables are described as frequencies and percentages and were analysed by the chi-square test. Missing data (\u0026lt;5%) were handled by complete-case analysis. The impact of EBP measures on adverse outcomes was assessed via logistic regression analysis. A multivariate logistic regression model was used to adjust for potential confounding factors, including gestational age, sex, birth weight, delivery mode, conception method, and a 1-minute Apgar score \u0026le;7. Adjusted results are reported with adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs). All the statistical analyses were conducted via SPSS Statistics 27.0, with a p value \u0026lt;0.05 considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eStudy population characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA total of 536 VPIs with a GA\u0026thinsp;\u0026lt;\u0026thinsp;32 weeks were included, with an overall median GA of 30.0 weeks and a median birth weight (BW) of 1245 g. These infants were stratified into SWMM (n\u0026thinsp;=\u0026thinsp;380) and severe complication/death (n\u0026thinsp;=\u0026thinsp;156) groups. Significant intergroup differences were observed: the severe complications/death group had lower GA (median 27.9 vs. 30.4 weeks, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and BW (median 960 g vs. 1360 g, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) values. Higher rates of assisted reproductive technology (26.3% vs. 18.0%, P\u0026thinsp;=\u0026thinsp;0.031), lower cesarean section rates (59.6% vs. 73.7%, P\u0026thinsp;=\u0026thinsp;0.001), and a higher proportion of patients with a 1-minute Apgar score\u0026thinsp;\u0026le;\u0026thinsp;7 (30.1% vs. 13.7%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were observed in the severe complications/death group. Sex, maternal age, hypertensive disorders, and a 5-minute Apgar score\u0026thinsp;\u0026le;\u0026thinsp;7 were not significantly different (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (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\u003eBaseline characteristics and outcomes\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables, n(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSWMM\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;380)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSevere complications/death(n\u0026thinsp;=\u0026thinsp;156)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal(n\u0026thinsp;=\u0026thinsp;536)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eχ\u003csup\u003e༒\u003c/sup\u003e/Z\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\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=\"left\" colname=\"c2\"\u003e\u003cp\u003e30.4(29.1,31.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27.9(26.1,29.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30(28.1,31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-10.574\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex, Male\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e212(55.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e101(64.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e313(58.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.056\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBirth Weight(g), median(IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1360(1130,1520)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e960(800,1200)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1245(990,1490)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-10.294\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esmall for gestational age\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17(4.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12(7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e29(5.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.239\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.135\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eART\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68(18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41(26.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e109(20.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.674\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.031*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emultiple pregnancy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e105(27.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46(29.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e151(28.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.641\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.726\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ematernal age(y), median(IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32(29,35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31(29,35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e31(29,35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026minus;0.795\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.426\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCesarean section\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e278(73.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e93(59.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e371(69.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e10.405\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGDM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e127(33.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39(25.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e166(31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e3.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.061\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHDP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e75(19.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33(21.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e108(20.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.143\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.705\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1-minute Apgar score\u0026thinsp;\u0026lt;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52(13.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47(30.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e99(18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e19.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5-minute Apgar score\u0026thinsp;\u0026lt;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11(2.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9(5.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20(3.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e6.275\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.111\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: SWMM, survival without major morbidity; GDM, gestational diabetes mellitus; HDP, hypertensive disorders of pregnancy; ART, assisted reproductive technology.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e* p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicates statistical significance.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eEvidence-Based Practices (EBPs) Adherence\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAdherence to EBPs was significantly different between the two groups. The severe complications/death group exhibited significantly lower adherence to key EBPs (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e): complete ACS (44.9% vs. 55.8%, P\u0026thinsp;=\u0026thinsp;0.021). DCC/UCM (4.9% vs. 18.5%, P\u0026thinsp;=\u0026thinsp;0.020); normothermia (36.5\u0026deg;C-37.5\u0026deg;C) within the first hour after birth (36.5% vs. 54.7%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001); caffeine administration rate within 48 hours after birth (88.3% vs. 94.3%, P\u0026thinsp;=\u0026thinsp;0.024); and enteral nutrition within 24 h (42.9% vs. 67.0%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). T-piece resuscitator use was greater in the severe complications/death group (75.8% vs. 65.8%, P\u0026thinsp;=\u0026thinsp;0.008), likely reflecting greater illness severity.\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\u003eOutcome Comparisons by Exposure to Specific Evidence-Based Practices (EBPs)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEBPs\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSWMM(n\u0026thinsp;=\u0026thinsp;380)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSevere complications/death(n\u0026thinsp;=\u0026thinsp;156)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;536)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eΧ\u003csup\u003e2\u003c/sup\u003e/Z\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\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\u003eACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e337(89.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e141(91.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e478(90.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.497\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComplete course of ACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e212(55.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e70(44.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e282(52.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.288\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.021*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMagnesium sulfate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e282(74.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e107(68.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e389(72.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.755\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.185\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInborn delivery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e376(98.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e150(96.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e526(98.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.04*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDCC/UCM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e99(18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e26(4.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e125(23.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.449\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.02*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT-piece use in the delivery room\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e235(65.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e113(75.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e348(68.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15.027\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNormothermia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e208(54.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e57(36.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e265(49.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14.653\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e165(43.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e119(76.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e284(53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e47.942\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInitial dose of PS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e173.9(142.9,200)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e179.8(142.4,200)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e176.5(142.9,200)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026minus;1.287\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.198\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCaffeine therepy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e335(88.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e137(87.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e472(88.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.913\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCaffeine within 48 hours after birth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e316(94.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e121(88.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e437(92.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.111\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.024*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEnteral feeding within 24 hours\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e238(67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e57(42.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e295(60.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23.671\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eAbbreviations: ACS, antenatal corticosteroids; DCC, deferring cord clamping; UCM, umbilical cord milking; PS, pulmonary surfactant.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e* p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicates a statistically significant difference.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the implementation of all or none of the five EBPs. Specifically, 52.6% (n\u0026thinsp;=\u0026thinsp;282) received a complete course of ACS, 72.6% (n\u0026thinsp;=\u0026thinsp;389) were administered antenatal MgSO\u003csub\u003e4\u003c/sub\u003e for fetal neuroprotection, 98.1% (n\u0026thinsp;=\u0026thinsp;526) were delivered at tertiary perinatal centers with RDS management capabilities, 49.4% (n\u0026thinsp;=\u0026thinsp;265) achieved normothermia (\u0026ge;\u0026thinsp;36.5\u0026deg;C) within the first hour after birth, and 88.1% (n\u0026thinsp;=\u0026thinsp;472) received caffeine therapy. However, only 19.2% (n\u0026thinsp;=\u0026thinsp;103) of the infants received all five EBPs concurrently (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAs the GA increased from \u0026lt;\u0026thinsp;24 weeks to 30\u0026ndash;31\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003eweeks, we observed increasing implementation trends for key EBPs: normothermia maintenance (33.3% \u0026rarr; 55.1%, P\u0026thinsp;=\u0026thinsp;0.043) and overall bundle adherence (0% \u0026rarr; 19.9%), although most EBPs showed no statistical significance (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\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 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eLogistic regression analyses examining the association of EBPs with severe complications/death\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\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCrude OR(95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP value\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\u003eComplete course of ACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.65(0.44,0.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.71(0.45,1.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.139\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMagnesium sulfate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.76(0.50,1.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.186\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.61(0.37,1.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.051\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInborn delivery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.27(0.07,0.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.042\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.18(0.04,0.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.032*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDCC/UCM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.57(0.35,0.92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.55(0.31,0.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.034*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNormothermia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.48(0.32,0.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.58(0.37,0.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.019*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCaffeine therepy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.97(0.55,1.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.913\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.06(0.51,2.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAll EBPs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.39(0.22,0.69)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.44(0.23,0.84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.013*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: OR, odds ratio; CI, confidence interval.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eAdjusted for gestational age, sex, birth weight, mode of conception, type of delivery, and 1-min Apgar score.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e* p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicates a statistically significant difference.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eImpact of EBPs on Outcomes\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMultivariate regression analysis (adjusted for gestational age, sex, birth weight, conception method, delivery mode, and 1-minute Apgar score\u0026thinsp;\u0026le;\u0026thinsp;7) revealed that three EBPs were significantly associated with a reduction in severe complications/deaths: delivery at centers with RDS management capabilities (aOR\u0026thinsp;=\u0026thinsp;0.18, 95% CI: 0.04\u0026ndash;0.86; P\u0026thinsp;=\u0026thinsp;0.032). DCC/UCM (aOR\u0026thinsp;=\u0026thinsp;0.55, 95% CI: 0.31\u0026ndash;0.96, P\u0026thinsp;=\u0026thinsp;0.034), and normothermia (36.5\u0026ndash;37.5\u0026deg;C) within the first hour after birth (aOR\u0026thinsp;=\u0026thinsp;0.58, 95% CI: 0.37\u0026ndash;0.91, P\u0026thinsp;=\u0026thinsp;0.019).\u003c/p\u003e\u003cp\u003eAlthough a complete course of ACS, antenatal MgSO\u003csub\u003e4\u003c/sub\u003e, and caffeine therapy demonstrated no independent protective effects after adjustment (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), concurrent implementation of all five EBPs significantly reduced adverse outcome risk (aOR\u0026thinsp;=\u0026thinsp;0.44, 95% CI: 0.23\u0026ndash;0.84, P\u0026thinsp;=\u0026thinsp;0.013).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe all-or-none assessment method enables effective evaluation of the implementation status and improvement opportunities for high-quality EBPs with extensive validation[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In this study, we applied the all-or-none approach to analyse the five EBPs. Our analysis demonstrated that VPIs receiving all EBPs presented a significantly reduced incidence of adverse outcomes (aOR\u0026thinsp;=\u0026thinsp;0.44; 95% CI: 0.23\u0026ndash;0.84; P\u0026thinsp;=\u0026thinsp;0.013). These findings indicate that the comprehensive implementation of high-quality evidence-based guidelines improves preterm infant prognosis and reduces adverse event rates. However, only 19.2% received the complete bundle, indicating significant gaps in quality improvement\u0026mdash;particularly for underperforming interventions such as normothermia within the first hour after birth (49.4%) and DCC/UCM (23.3%), which demonstrated critically low implementation rates in this study.\u003c/p\u003e\u003cp\u003eThe five EBPs bundled in our study have each been proven to improve the clinical outcomes of VPIs. For the first EBPs (inborn deliveries at centers with RDS management capabilities), many studies have shown that birth in a maternity unit, which is termed a level III hospital, is associated with better outcomes for VPIs[\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. All nine included hospitals were Level 3 facilities, where 98.1% of deliveries occurred. VPIs born at these hospitals demonstrated a significantly reduced incidence of adverse outcomes (aOR\u0026thinsp;=\u0026thinsp;0.18; 95% CI: 0.04\u0026ndash;0.86; P\u0026thinsp;=\u0026thinsp;0.032). For the second practice (complete course of ACS), meta-analyses of observational studies have shown that ACS reduces the risk of perinatal death (RR\u0026thinsp;=\u0026thinsp;0.85, 95% CI: 0.77\u0026ndash;0.93) neonatal death (RR\u0026thinsp;=\u0026thinsp;0.78, 95% CI: 0.70\u0026ndash;0.87; RDS (RR\u0026thinsp;=\u0026thinsp;0.71, 95% CI: 0.65\u0026ndash;0.78)) and probably reduces the risk of IVH (RR\u0026thinsp;=\u0026thinsp;0.58, 95% CI: 0.45\u0026ndash;0.75). The administration rate for infants born at \u0026lt;\u0026thinsp;32 weeks ranges from 82\u0026ndash;93% in developed countries [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In China, a large-scale survey reported an ACS utilization rate of 78.0%, with only 49.1% of these cases receiving a complete course [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Our study revealed higher rates: 90.2% for ACS administration and 52.6% for the complete course. These figures exceed China's national averages and approach those documented in developed countries. The dosage, treatment course completeness, and timing of ACS administration may all potentially impact outcomes in VPIs[\u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In our study, although the group receiving a complete course of ACS demonstrated a significantly lower incidence of adverse outcomes than the SWMM group did, the aOR was not significantly different. This may be attributed to our composite outcome incorporating multiple severe complications, which potentially weakened the association between ACS exposure and individual adverse outcomes. For third-EBPs (antenatal MgSO\u003csub\u003e4\u003c/sub\u003e), substantial evidence confirms that antenatal MgSO\u003csub\u003e4\u003c/sub\u003e administration reduces the risk of cerebral palsy, although it has no significant association with overall infant mortality[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Although not associated with short-term clinical outcomes, MgSO₄ remains recommended as standard practice because of its established association with significantly reduced long-term neurodevelopmental sequelae such as cerebral palsy. Similarly, in our study, MgSO₄ was not significantly associated with short-term outcomes. However, when evaluated through the all-or-none composite assessment, it contributes to improved preterm infant outcomes when it is implemented collectively with other evidence-based interventions. MgSO\u003csub\u003e4\u003c/sub\u003e administration increased from 65.8% in 2017 to 85.5% in 2022 in England[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In our study, the administration rate of MgSO₄ was 72.6%, indicating the ongoing potential for improvement. Our fourth evidence-based practice targeted the maintenance of normothermia within the first hour after birth. A recent systematic review published in Pediatrics demonstrated that the mean hypothermia rate was 42% (range 14%-88%), and hypothermia was associated with increased mortality (aOR\u0026thinsp;=\u0026thinsp;1.55, 95% CI: 1.29\u0026ndash;1.87)[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In our study, maintaining normothermia within the first hour after birth similarly demonstrated a reduced likelihood of the composite outcome of severe adverse events or mortality in VPIs (aOR\u0026thinsp;=\u0026thinsp;0.58; 95% CI: 0.37\u0026ndash;0.91). However, the observed incidence rate of hypothermia (50.6%) remained higher than the benchmark rates, necessitating targeted improvement initiatives. For the fifth evidence-based practice (caffeine therapy), meta-analyses indicate that caffeine administration reduces the incidence of BPD [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] and decreases the risk of extubation failure [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. However, the optimal timing for caffeine initiation remains debated [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Our study revealed that, compared with the SWMM group, the severe complications/death group had significantly lower caffeine administration rates within 48 hours after birth (88.3% vs. 94.3%; P\u0026thinsp;=\u0026thinsp;0.024).\u003c/p\u003e\u003cp\u003eAs gestational age advances, the implementation rates of EBPs tend to increase (e.g., normothermia increased from 33.3\u0026ndash;55.1%). However, all EBP coverage remained near zero for periviable infants (\u0026lt;\u0026thinsp;24 weeks) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e3\u003c/span\u003e). This cohort has an adverse outcome rate as high as 88.9%, indicating a gap compared with international benchmarks. A meta-analysis revealed substantial disparities in the survival rates of extremely immature infants at 22\u0026ndash;25 weeks gestation across different economic settings[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], highlighting global inequities in perinatal health. Sustained research and collaborative efforts remain crucial to further improve global survival and long-term outcomes for infants with survival potential.\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 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEBPs and outcomes by gestational age\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;24\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24\u0026ndash;26\u0026thinsp;\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27\u0026ndash;29\u0026thinsp;\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e30\u0026ndash;31\u0026thinsp;\u003csup\u003e+\u0026thinsp;6\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eΧ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\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\u003eComplete course of ACS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28(46.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e97(50.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e154(55.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e3.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.313\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMagnesium sulfate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5(55.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44(73.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e144(75.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e196(71.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.554\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.456\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInborn delivery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59(98.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e186(97.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e272(98.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.318\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.773\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDCC/UCM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14(23.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e46(24.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e65(23.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.583\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.473\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNormothermia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24(40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e86(45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e152(55.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e8.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.043*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCaffeine therepy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6(66.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51(85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e175(91.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e240(87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e6.971\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.061\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAll EBPs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9(15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e38(19.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e56(20.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.553\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.457\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSevere complications/death\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8(88.9)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47(78.3)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70(36.6)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e31(11.2)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e131.217\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e* p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicates a statistically significant difference.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThere are several limitations in this study. First, we included only facilities with \u0026gt;\u0026thinsp;20 VPI cases in the SNDN database. All nine sites were tertiary hospitals, limiting the generalizability of the conclusions to primary care settings. Second, the exclusion of transferred patients lost to follow-up may have introduced selection bias in the implementation rates. Third, the retrospective design resulted in a reliance on medical record completeness for certain EBPs. For example, DCC implementation rates may be artificially low because of potential underreporting. A. Rizzolo et al. demonstrated that DCC synergistically reduces neonatal mortality when combined with other EBPs[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A meta-analysis provided high-certainty evidence that DCC reduces death before discharge in preterm infants[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Similarly, our study revealed that DCC/UCM reduces adverse outcomes (aOR\u0026thinsp;=\u0026thinsp;0.55; 95% CI: 0.31\u0026ndash;0.96). However, its limited sample size precluded inclusion in the bundle analysis. Fourth, our study population was limited in terms of short-term outcomes up to hospital discharge, precluding analysis of long-term neurodevelopmental outcomes.\u003c/p\u003e\u003cp\u003eIn summary, we demonstrated that bundle implementation of EBPs significantly reduces adverse outcomes in VPIs. Adherence to these practices can serve as a metric for evaluating a healthcare facility's quality of care and provide actionable insights for quality improvement. Nevertheless, the overall implementation rate of EBPs remains suboptimal, highlighting persistent challenges in translating effective interventions into routine clinical practice. Barriers include gaps in clinicians' knowledge and attitudes, organizational obstacles within units, and limitations in facility resources. Substantial opportunities exist for quality enhancement\u0026mdash;by systematically improving EBP implementation rates, we can ultimately increase SWMM in this vulnerable population.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eBundled implementation of EBPs significantly improves clinical outcomes in VPIs. However, suboptimal adherence\u0026mdash;particularly for normothermia within the first hour after birth and DCC/UCM\u0026mdash;necessitates targeted quality improvement initiatives. We can enhance quality and improve SWMM in VPIs by systematically improving the implementation rates of EBPs.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eVPIs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eVery Preterm Infants\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSWMM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003esurvival without major morbidity\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEBPs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eevidence-based practices\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSNDN\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eShenzhen Neonatal Data Network\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\"\u003eBW\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ebirth weight\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRDS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003erespiratory distress syndrome\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDCC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003edeferring cord clamping\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eUCM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eumbilical cord milking\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eACS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eantenatal corticosteroids\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMgSO4\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003emagnesium sulfate\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGDM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003egestational diabetes mellitus\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHDP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ehypertensive disorders of pregnancy\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eART\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eassisted reproductive technology\u003c/p\u003e\u003c/div\u003e\u003c/div\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\"\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\"\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\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the International Conference on Good Clinical Practice standards and the Declaration of Helsinki. The study received approval from the Ethics Committee of Longgang District Maternity \u0026amp; Child Healthcare Hospital of Shenzhen City (approval number: LGFYKYXMLL-2025-42) and was recognized by the ethics committees of all the participating institutions. Informed consent was waived at each site because the use of deidentified patient data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp skip=\"true\"\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors want to thank all the participants in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJF conducted all\u0026nbsp;the data analyses and was the primary contributor to the writing of the manuscript. CC, HT and XG contributed to the conception and design of this study. RL and ZY offered clinical insights for interpreting the results. HC, YL, KZ, DR, GD and XY contributed to the acquisition, analysis and interpretation of the data. All the authors reviewed the manuscript and gave permission to be published.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp skip=\"true\"\u003eThis research received no specific grant from any funding agency.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during this study are available from the corresponding author\u0026nbsp;upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data in this study were provided by nine member hospitals of the SNDN, with participating institutions listed in alphabetical order as follows: Longgang District Maternity \u0026amp; Child Healthcare Hospital of Shenzhen City,Peking University Shenzhen Hospital,Shenzhen People\u0026apos;s Hospital,Shenzhen Baoan District Maternity and Child Healthcare Hospital,Shenzhen Longgang District Central Hospital,Shenzhen Longhua District People\u0026rsquo;s Hospital,Shenzhen Longhua Maternity and Child Healthcare Hospital,Shenzhen Luohu People\u0026apos;s Hospital,The People\u0026rsquo;s Hospital of Baoan Shenzhen.\u003cbr\u003e \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChen C, Zhang JW, Xia HW, Zhang HX, Betran AP, Zhang L, et al. Preterm Birth in China Between 2015 and 2016. Am J Public Health. 2019;109(11):1597\u0026ndash;604.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eD'Apremont I, Marshall G, Musalem C, Mariani G, Musante G, Bancalari A, et al. Trends in Perinatal Practices and Neonatal Outcomes of Very Low Birth Weight Infants during a 16-year Period at NEOCOSUR Centers. J Pediatr. 2020;225:44\u0026ndash;e501.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYounge N, Goldstein RF, Bann CM, Hintz SR, Patel RM, Smith PB, et al. Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med. 2017;376(7):617\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOhuma EO, Moller AB, Bradley E, Chakwera S, Hussain-Alkhateeb L, Lewin A, et al. National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis. Lancet. 2023;402(10409):1261\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee SK, Beltempo M, McMillan DD, Seshia M, Singhal N, Dow K, et al. Outcomes and care practices for preterm infants born at less than 33 weeks' gestation: a quality-improvement study. CMAJ. 2020;192(4):E81\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYan C, Gong X, Luo H, Liu Y, Lin Y, Weng B, et al. Impact of implementation of 2019 European respiratory distress syndrome guidelines on bronchopulmonary dysplasia in very preterm infants. Ital J Pediatr. 2024;50(1):178.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGarc\u0026iacute;a-Mu\u0026ntilde;oz Rodrigo F, Fabres J, Tapia JL, D'Apremont I, San Feliciano L, Zozaya Nieto C, et al. Factors Associated with Survival and Survival without Major Morbidity in Very Preterm Infants in Two Neonatal Networks: SEN1500 and NEOCOSUR. Neonatology. 2021;118(3):289\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSweet DG, Carnielli VP, Greisen G, Hallman M, Klebermass-Schrehof K, Ozek E, et al. European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update. Neonatology. 2023;120(1):3\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eT TNN, DM DMBB. All-or-none measurement raises the bar on performance. JAMA. 2006(10):1168\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePapile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978;92(4):529\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFanaroff AA, Hack M. Periventricular leukomalacia\u0026ndash;prospects for prevention. N Engl J Med. 1999;341(16):1229\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163(7):1723\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187(1):1\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChiang MF, Quinn GE, Fielder AR, Ostmo SR, Paul Chan RV, Berrocal A, et al. International Classification of Retinopathy of Prematurity, Third Edition. Ophthalmology. 2021;128(10):e51\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGarc\u0026iacute;a-Mu\u0026ntilde;oz Rodrigo F, D\u0026iacute;ez Recinos AL, Garc\u0026iacute;a-Alix P\u0026eacute;rez A, Figueras Aloy J, Vento Torres M. Changes in perinatal care and outcomes in newborns at the limit of viability in Spain: the EPI-SEN Study. Neonatology. 2015;107(2):120\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRizzolo A, Shah PS, Boucorian I, Lemyre B, Bertelle V, Pelausa E et al. Cumulative effect of evidence-based practices on outcomes of preterm infants born at \u0026lt;\u0026thinsp;29 weeks' gestational age. Am J Obstet Gynecol. 2020;222(2):181.e1-.e10.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZeitlin J, Manktelow BN, Piedvache A, Cuttini M, Boyle E, van Heijst A, et al. Use of evidence based practices to improve survival without severe morbidity for very preterm infants: results from the EPICE population based cohort. BMJ. 2016;354:i2976.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWarner B, Musial MJ, Chenier T, Donovan E. The effect of birth hospital type on the outcome of very low birth weight infants. Pediatrics. 2004;113(1 Pt 1):35\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLasswell SM, Barfield WD, Rochat RW, Blackmon L. Perinatal regionalization for very low-birth-weight and very preterm infants: a meta-analysis. JAMA. 2010;304(9):992\u0026ndash;1000.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAli AA, Naseem HA, Allahuddin Z, Yasin R, Azhar M, Hanif S, et al. The Effectiveness of Regionalization of Perinatal Care and Specific Facility-Based Interventions: A Systematic Review. Neonatology. 2025;122(Suppl 1):245\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcGoldrick E, Stewart F, Parker R, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2020;12(12):Cd004454.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhao J, Feng Z, Dai Y, Zhang W, Jiang S, Wang Y, et al. Use of antenatal corticosteroids among infants with gestational age at 24 to 31 weeks in 57 neonatal intensive care units of China: a cross-sectional study. Chin Med J (Engl). 2023;136(7):822\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchmitz T, Doret-Dion M, Sentilhes L, Parant O, Claris O, Renesme L, et al. Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial. Lancet. 2022;400(10352):592\u0026ndash;604.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBlickstein I, Reichman B, Lusky A, Shinwell ES. Plurality-dependent risk of severe intraventricular hemorrhage among very low birth weight infants and antepartum corticosteroid treatment. Am J Obstet Gynecol. 2006;194(5):1329\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBattarbee AN, Ros ST, Esplin MS, Biggio J, Bukowski R, Parry S, et al. Optimal timing of antenatal corticosteroid administration and preterm neonatal and early childhood outcomes. Am J Obstet Gynecol MFM. 2020;2(1):100077.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFuma K, Kotani T, Tsuda H, Oshiro M, Tano S, Ushida T, et al. Impact of antenatal corticosteroids-to-delivery interval on very preterm neonatal outcomes: a retrospective study in two tertiary centers in Japan. BMC Pregnancy Childbirth. 2024;24(1):607.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eConde-Agudelo A, Romero R. Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks' gestation: a systematic review and metaanalysis. Am J Obstet Gynecol. 2009;200(6):595\u0026ndash;609.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShepherd ES, Goldsmith S, Doyle LW, Middleton P, Marret S, Rouse DJ, et al. Magnesium Sulfate Before Preterm Birth for Neuroprotection: An Updated Cochrane Systematic Review. Obstet Gynecol. 2024;144(2):161\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEdwards HB, Sillero-Rejon C, McLeod H, Hill EM, Opmeer BC, Peters C et al. Implementation of national guidelines on antenatal magnesium sulfate for neonatal neuroprotection: extended evaluation of the effectiveness and cost-effectiveness of the National PReCePT Programme in England. BMJ Qual Saf. 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHogeveen M, Hooft L, Onland W. Hypothermia and Adverse Outcomes in Very Preterm Infants: A Systematic Review. Pediatrics. 2025;155(5).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKua KP, Lee SW. Systematic review and meta-analysis of clinical outcomes of early caffeine therapy in preterm neonates. Br J Clin Pharmacol. 2017;83(1):180\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFerguson KN, Roberts CT, Manley BJ, Davis PG. Interventions to Improve Rates of Successful Extubation in Preterm Infants: A Systematic Review and Meta-analysis. JAMA Pediatr. 2017;171(2):165\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNylander Vujovic S, Nava C, Johansson M, Bruschettini M. Confounding biases in studies on early- versus late-caffeine in preterm infants: a systematic review. Pediatr Res. 2020;88(3):357\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi YX, Hu YL, Huang X, Li J, Li X, Shi ZY, et al. Survival outcomes among periviable infants: a systematic review and meta-analysis comparing different income countries and time periods. Front Public Health. 2024;12:1454433.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSeidler AL, Aberoumand M, Hunter KE, Barba A, Libesman S, Williams JG, et al. Deferred cord clamping, cord milking, and immediate cord clamping at preterm birth: a systematic review and individual participant data meta-analysis. Lancet. 2023;402(10418):2209\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Evidence-based practices, Very preterm infants, Outcome, Mortality, Survival without major morbidity","lastPublishedDoi":"10.21203/rs.3.rs-7249012/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7249012/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground Although evidence-based practices (EBPs) can improve outcomes in very preterm infants (VPIs), real-world implementation rates and evidence regarding their synergistic effects remain limited. This study, which is based on the Shenzhen Neonatal Data Network (SNDN), evaluated the current implementation status of EBPs and the impact of their synergistic effects on clinical outcomes.\u003c/p\u003e\n\u003cp\u003eMethods We conducted a retrospective study on 536 VPIs with a gestational age \u0026lt;32 weeks in 2024. These infants were categorized into asurvival without major morbidity (SWMM) group and an adverse outcome group (severe complications/death), with differences in the implementation of evidence-based practices (EBPs) evaluated between the two groups. Using the \"all-or-none\" approach, we further assessed five core EBPs: delivery at an experienced perinatal center; complete course of antenatal corticosteroids (ACS); antenatal magnesium sulfate (MgSO₄); maintenance of normothermia (36.5°C--37.5°C) within one hour after birth; and caffeine therapy.Multivariate logistic regression analysis was employed to explore the associationsbetween EBP implementation and adverse outcomes.\u003c/p\u003e\n\u003cp\u003eResults Bundle implementation of five EBPs significantly reduced adverse outcomes in VPIs (aOR=0.47, 95% CI: 0.25–0.90). Independent protective factors included delivery at RDS-experienced centers (aOR=0.18, 95% CI: 0.04–0.86); delayed cord clamping (DCC)/umbilical cord milking (UCM) (aOR=0.55, 95% CI: 0.31–0.96);and normothermia within the first hour after birth (aOR=0.58, 95% CI: 0.37–0.91). Only 19.2% of VPIs received all five EBPs. The lowestimplementation rates were reported for normothermia within the first hour after birth (49.4%) and DCC/UCM (23.3%).\u003c/p\u003e\n\u003cp\u003eConclusions Bundled implementation of EBPs significantly improves clinical outcomes in VPIs. However, suboptimal adherence—particularly for normothermia within the first hour after birth and DCC/UCM—necessitates targeted quality improvement initiatives. We can enhance quality and improve SWMM in VPIs by systematically improving the implementation rates of EBPs.\u003c/p\u003e","manuscriptTitle":"Impact of Evidence-Based Practice Bundles on Clinical Outcomes in Very Preterm Infants: A Multicenter Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-19 11:58:51","doi":"10.21203/rs.3.rs-7249012/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ac27af14-f2ab-4d33-bca8-db15923d3aee","owner":[],"postedDate":"November 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-08T14:34:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-19 11:58:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7249012","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7249012","identity":"rs-7249012","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}