Risk factors for early periventricular intraventricular hemorrhage in extremely low birth weight infants: a retrospective study

Risk factors for early periventricular intraventricular hemorrhage in extremely low birth weight infants: a 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Risk factors for early periventricular intraventricular hemorrhage in extremely low birth weight infants: a retrospective study Yueju Cai, Yongjiang Jiang, Ping Wang, Xiaopeng Zhao, Yanyan Song, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4286126/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 This study aimed to explore the risk factors for early periventricular intraventricular hemorrhage (PIVH) in extremely low birth weight infants (ELBWIs), provide guidance for early intervention, and improve the survival rate and life expectancy of ELBWIs. Methods A retrospective study was conducted on 205 ELBWIs admitted to the Women and Children's Medical Center of Guangzhou Medical University from January 2019 to December 2023. The presence and severity of PIVH were assessed through standard head ultrasound screening (HUS) using the modified Papile classification on days 1–3 and 5–7 postbirth. The infants were categorized into either the PIVH group or the non-PIVH group based on the HUS findings. Univariate analysis and logistic regression were employed to identify the risk factors associated with PIVH. The efficacy of the model was evaluated using a receiver operating characteristic (ROC) curve. Results Among the 205 ELBWIs (97 males and 108 females) included in the study, 82 patients (40.0%) developed PIVH, 26 patients (12.7%) had severe PIVH, and 56 patients (27.3%) had mild PIVH. Of the 82 PIVH cases, 51 occurred within 3 days after birth. The incidence rates of severe PIVH in the 23 + 1 -26-, 26 + 1 -28-, and 28 + 1 -32-week gestational age groups were 40.0% (16/40), 10.7% (10/93), and 1.4% (1/72), respectively (χ2 = 34.392, p = 0.000). Logistic regression analysis revealed that failure to withdraw invasive ventilators within 1 week (OR = 3.668, 95% CI = 1.557–8.641, p = 0.003) and the use of vasoactive drugs within 1 week (OR = 2.193, 95% CI = 1.033–4.658, p = 0.041) were independent risk factors for PIVH (sensitivity = 68.3%).The specificity was 81.3%, and the AUC was 0.792. Conclusion The incidence of PIVH in extremely low birth weight infants is relatively high, particularly within the first three days after birth. The use of vasoactive drugs and delayed removal of invasive ventilators may increase the risk. Risk factors Periventricular hemorrhage Extremely low birth weight infants Incidence Preterm Figures Figure 1 Figure 2 Background Extremely low birth weight infants (ELBWIs) are those who weigh less than 1000 g at birth. With advancements and progress in perinatal medicine, there has been a significant increase in the survival rate of premature infants, particularly ELBWIs[ 1 ]. Periventricular intraventricular hemorrhage (PIVH) is a common complication in premature infants, with a higher incidence and severity observed in those born at earlier gestational ages[ 2 ]. ELBWIs have underdeveloped organs and are prone to unstable conditions, making them highly vulnerable to PIVH, which often presents with subtle, challenging-to-detect symptoms early on. PIVH can lead to developmental delays, cognitive impairments, epilepsy, disabilities, and even death, significantly impacting parents' treatment decisions and the long-term quality of life of children[ 3 – 7 ]. The pathogenesis of PIVH is multifaceted, with few available treatment options and a poor prognosis. PIVH typically peaks during the first week after birth, particularly within the first 3 days[ 8 , 9 ]. Despite several studies on the risk factors for PIVH in premature infants[ 10 – 14 ], research on the early prediction and risk factors for early-stage PIVH in ELBWIs is scarce, posing challenges to their prevention and management. Our study was a retrospective analysis of data from ELBWIs admitted to our institution. The objective was to identify risk factors for PIVH in the early stages of life among ELBWIs. The purpose of this study is to provide recommendations for implementing timely interventions to increase the survival rate and quality of life of ELBWIs. Methods Patients A retrospective study of ELBWIs admitted to the Women and Children's Medical Center of Guangzhou Medical University from January 2019 to December 2023 was conducted. The inclusion criteria were as follows: 1) admission to the NICU within 24 hours after birth, 2) birth weight < 1000 g, and 3) head ultrasound (HUS) performed on days 1–3 and 5–7 postbirth. Premature infants with structural organ abnormalities, congenital metabolic diseases, and chromosomal abnormalities and those who died or were discharged within 7 days after birth were excluded. Based on the HUS results, the subjects were categorized into the PIVH group and the non-PIVH group (Fig. 1 ). The study was approved by the Ethics Committee of Women and Children Medical Center Affiliated with Guangzhou Medical University (No. 350B00) in accordance with ethical guidelines. Informed consent was not required for this retrospective study, which was approved by the Ethics Committee. Delivery room management for premature infants Prior to the delivery of premature infants, pediatricians and obstetricians collaborate to develop treatment plans, engage in discussions with family members regarding the infants' condition, and obtain informed consent. The pediatric team is present in the delivery room before birth and is ready for use with preresuscitation equipment. Immediately after birth, it is crucial to ensure that premature infants are kept warm, their airways are cleared of secretions, and they are provided with CPAP support. Once stabilized, the infant is promptly transferred to the NICU for ongoing monitoring and treatment. Pulmonary surfactant (PS) is administered in the NICU via MIST. Infants not requiring tracheal intubation receive noninvasive respiratory support. Ultrasound Skilled attending physicians in the ultrasound department utilized the Philips Epiq5 color Doppler ultrasound system (Philips Ultrasound, Inc., Washington, USA) to perform HUS exams on newborns on days 1–3 and 5–7 postbirth. The severity of the PIVH was assessed based on the Papile system. PIVH is divided into four grades according to the PIVH diagnosis and Papile classification criteria: Grade I - subependymal hemorrhage; Grade II - intraventricular hemorrhage, covering 10–50% of the area; Grade III - intraventricular hemorrhage with ventricular enlargement, bleeding area exceeding 50%; Grade IV - intraventricular hemorrhage with ventricular enlargement and cerebral parenchymal hemorrhage. Grades I and II are considered mild, while grades III and IV are categorized as severe PIVH. Data collection The medical records of the infants were reviewed during hospitalization to document important information such as sex, gestational age, birth weight, mode of delivery, place of delivery, IVF status, presence of twins, premature rupture of membranes, characteristics of amniotic fluid, use of prenatal glucocorticoids, and magnesium sulfate. Maternal complications such as gestational diabetes and hypertension, intrauterine distress, intrauterine infection, threatened preterm labor, resuscitation measures during delivery (including resuscitation for asphyxiation, endotracheal intubation, chest compressions, and pure oxygen resuscitation), 1-minute and 5-minute Apgar scores, failure to withdraw invasive ventilators within 1 week, use of high frequency oscillatory ventilation (HFOV) for at least 24 hours, administration of vasoactive drugs, nitric oxide (NO), and PS treatment, occurrence of sepsis, presence of PDA and treatment with ibuprofen, anemia and blood transfusion status, and presence of coagulation disorders and thrombocytopenia were also documented. Statistical methods SPSS software, version 25.0 from IBM Corp. in Armonk, NY, was utilized for performing the statistical analysis. The presentation of the data varied depending on their distribution, with the mean and standard deviation or median and interquartile range (IQR) being used. The frequency data are presented as numbers (n) and percentages (%). Group differences were evaluated using the independent sample t test for normally distributed variables and the Mann–Whitney U test for nonnormally distributed variables. Categorical variables were analyzed using the chi-square test. The risks associated with PIVH were determined through logistic regression analysis. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the model. An area under the curve (AUC) greater than 0.75 indicates high discrimination. The Hosmer‒Lemeshow test was used to calibrate the model. The significance level was set at p < 0.05, which suggests a good model fit with no significant difference between the predicted and true values. Results Demographic characteristics of the ELBWI in the PIVH and non-PIVH groups A total of 205 ELBWIs, including 97 males and 108 females, were included in this study, with a male to female ratio of 0.90:1. Among them, 190 patients (92.7%) were born at our hospital, and 15 patients (7.3%) were born at other hospitals. The mean gestational age of the ELBWIs was 27.3 (26.5, 28.6) weeks, and the mean birth weight was 870 (750, 950) grams. There were 82 cases (40%) of PIVH, of which 51 cases (62.2%) occurred within 3 days after birth and 31 cases (37.8%) occurred within 4 to 7 days after birth. Among the 205 ELBWIs, 26 (12.6%) had severe PIVH, and 56 (27.3%) had mild PIVH. The incidence rates of PIVH in the 23 + 1 -26-, 26 + 1 -28-, and 28 + 1 -32-week groups were 72.5% (29/40), 33.3% (31/93), and 30.6% (22/72), respectively, and the difference was statistically significant (χ2 = 22.002, p = 0.000). The incidence rates of severe PIVH in the 23 + 1 -26-, 26 + 1 -28-, and 28 + 1 -32-week groups were 40.0% (16/40), 10.7% (10/93), and 1.4% (1/72), respectively, and the difference was statistically significant (χ2 = 34.392, p = 0.000). Compared to the non-PIVH group, the PIVH group had a significantly younger gestational age and lower birth weight (p = 0.000 and p = 0.021, respectively). In the PIVH group, 59.8% of infants were delivered by cesarean section, while in the non-PIVH group, this percentage was 28.5% (p = 0.000). Additionally, 56.1% (46/82) of infants in the PIVH group required resuscitation at birth (p = 0.003), and 47.6% (39/82) needed endotracheal intubation in the delivery room (p = 0.001). The median 1-minute Apgar score was 7 (5,8) in the PIVH group and 8 (6,8) in the non-PIVH group (p = 0.003). No significant differences in sex, place of delivery, IVF status, presence of twins, premature rupture of membranes, presence of amniotic fluid, fetal distress, 5-minute Apgar score, chest compressions in the delivery room, threatened preterm labor, antenatal use of glucocorticoids, antenatal use of MgSO4, intrauterine infection, gestational diabetes mellitus or gestational hypertension were found between the PIVH group and the non-PIVH group (all p > 0.05, Table 1 ). Table 1 Demographic characteristics of extremely low birth weight infants in PIVH and non-PIVH groups Values PIVH(n = 82) Non-PIVH(n = 123) χ2/Z p Sex Male Female 41(50.0) 41(50.0) 56(45.5) 67(54.5) 0.395 0.530 Gestational age 27(25.6,28.2) 27.5(27,29) −4.100 0.000 Birth weight 835(700,940) 890(780,950) −2.312 0.021 Mode of delivery Vaginal delivery Cesarean section 33(40.2) 49(59.8) 88(71.5) 35(28.5) 19.931 0.000 Delivery site In-born Out-born 74(90.2) 8 (9.8) 116(94.3) 7(5.7) 1.199 0.274 Multiple pregnancy Yes No 25(30.5) 57(69.5) 39(31.7) 84(68.3) 0.034 0.854 IVF Yes No 19(23.2) 63(76.8) 21(17.1) 102(82.9) 1.165 0.280 Premature rupture of membranes Yes No 16(19.5) 66(80.5) 38(30.9) 85(69.1) 3.285 0.070 Stained amniotic fluid Yes No 10(12.2) 72(87.8) 17(13.8) 106(86.2) 0.114 0.736 Fetal distress Yes No 14(17.1) 68(82.9) 19(15.4) 104(84.6) 0.096 0.756 Resuscitation at birth Yes No 46(56.1) 36(43.9) 43(35.0) 80(65.0) 8.949 0.003 Apgar score 1- minute 5- minute 7(5,8) 8(8,9) 8(6,8) 9(8,9) −2.954 −1.437 0.003 0.151 Chest compressions in delivery room Yes No 5(6.1) 77(93.9) 7(5.7) 116(94.3) 0.000 1.000 Intubated in delivery room Yes No 39(47.6) 43(52.4) 32(26.0) 91(74.0) 10.088 0.001 Threatened preterm labor Yes No 56(68.3) 26(31.7) 78(63.4) 45(36.6) 0.517 0.472 Antenatal use of glucocorticoids Yes No 47(57.3) 35(42.7) 84(68.3) 39(31.7) 2.569 0.109 Antenatal use of MgSO4 Yes No 38(46.3) 44(53.7) 67(54.5) 56(45.5) 1.302 0.254 Intrauterine infection Yes No 8(9.8) 74(90.2) 10(8.1) 113(91.9) 0.162 0.687 Gestational diabetes mellitus Yes No 13(15.9) 69(84.1) 20(16.3) 103(83.7) 0.006 0.938 Gestational hypertension Yes No 16(19.5) 66(80.5) 38(30.9) 85(69.1) 3.285 0.070 Treatments and Complications of the ELBWI in the PIVH and Non-PIVH Groups Compared to the non-PIVH group, the PIVH group had a greater percentage of infants who could not be weaned off the ventilator within 1 week of birth (73.0% vs. 30.1%, p = 0.000). Moreover, a larger proportion of infants in the PIVH group needed high-frequency ventilators for more than 24 hours (34.1% vs. 8.1%, p = 0.000), as well as nitric oxide (13.4% vs. 0.8%, p = 0.001) and vasoactive drugs (50.0% vs. 18.7%, p = 0.000). The incidence of sepsis and the requirement for blood transfusions to address anemia were also greater in the PIVH group (28.0% vs. 8.9%, p = 0.000, and 48.8% vs. 26.0%, p = 0.001, respectively). Nevertheless, there were no significant differences in the occurrence of PS use, PDA, anemia, coagulation disorders, or thrombocytopenia between the two groups. (all p < 0.05, Table 2 ). Table 2 Treatments and Complications of ELBWI in PIVH and Non-PIVH groups Values PIVH(n = 82) Non-PIVH(n = 123) χ2 p Failure to withdraw IMV Yes No 60(73.2) 22(26.8) 37(30.1) 86(69.9) 36.645 0.000 Use of HFOV for at least 24 hours Yes No 28(34.1) 54(65.9) 10(8.1) 113(91.9) 22.053 0.000 Use of NO Yes No 11(13.4) 71(86.6) 1 (0.8) 122(99.2) 11.983 0.001 Use of PS Yes No 71(86.6) 11(13.4) 96(78.0) 27(22.0) 2.374 0.123 Use of Vasoactive drugs Yes No 41(50.0) 41(50.0) 23(18.7) 100(81.3) 22.448 0.000 Sepsis Yes No 23(28.0) 59(72.0) 11(8.9) 112(91.1) 12.981 0.000 PDA Yes No 53(64.6) 29(35.4) 67(54.5) 56(45.5) 2.094 0.148 Ibuprofen treatment for PDA Yes No 2 (2.4) 80(97.6) 7 (5.7) 116(94.3) 0.586 0.444 Anemia Yes No 64(78.0) 18(22.0) 81(65.9) 42(34.1) 3.534 0.060 Blood transfusion for anemia Yes No 40(48.8) 42(51.2) 32(26.0) 91(74.0) 11.189 0.001 Coagulation dysfunction Yes No Unknown 10(12.2) 13(15.9) 59(72.0) 8 (6.5) 28(22.8) 87(70.7) 3.000 0.223 Thrombopenia Yes No 50(61.0) 32(39.0) 72(58.5) 51(41.5) 0.121 0.727 IMV: invasive mechanical ventilation, HFOV: high frequency oscillatory ventilation, NO: nitric oxide, PS: pulmonary surfactant, PDA: patent ductus arteriosus Risk factors and prediction for PIVH in the ELBWI The studies included significant risk factors in the univariate analysis, such as gestational age, birth weight, mode of delivery, resuscitation at birth, 1-minute Apgar score, intubation in the delivery room, failure to withdraw IMV within 1 week of birth, use of HFO for at least 24 hours, use of NO, use of vasoactive drugs, sepsis, and blood transfusion for anemia. According to the multivariable logistic regression analysis, failure to withdraw IMV within 1 week of birth (OR = 3.668, 95% CI = 1.557–8.641; P = 0.003) and the use of vasoactive drugs (OR = 2.193, 95% CI = 1.033–4.658; P = 0.041) were identified as independent risk factors for PIVH, as detailed in Table 3 . Analysis of the ROC curve demonstrated that the model achieved an AUC of 0.792 (95% CI 0.726–0.857), with a maximum Youden index of 0.496. The sensitivity and specificity were calculated to be 68.3% and 81.3%, respectively, as illustrated in Fig. 2 . The omnibus test revealed that the current model significantly outperformed the null model (χ2 = 58.304, p < 0.001). Additionally, the Hosmer & Lemeshow test (χ2 = 7.041, p = 0.532) indicated that the model fit the data accurately. Table 3 Analysis of risk factors for PIVH in ELBWI Variables β SE Wald χ2 OR (95% CI) P value Gestational age -0.116 0.139 0.702 0.890(0.678–1.169) 0.402 Birth weight 0.000 0.001 0.018 1.000(0.997–1.003) 0.892 Mode of delivery -0.022 0.419 0.003 0.978(0.430–2.224) 0.958 Resuscitation at birth 0.761 0.536 2.017 2.140(0.749–6.114) 0.156 1-minute Apgar score 0.164 0.144 1.292 1.178(0.888–1.564) 0.256 Intubated in delivery room 0.213 0.445 0.228 1.237(0.517–2.962) 0.633 Failure to withdraw IMV 1.300 0.437 8.838 3.668(1.557–8.641) 0.003 Use of HFOV for at least 24 hours 0.612 0.500 1.495 1.844(0.692–4.916) 0.221 Use of NO 1.596 1.160 1.890 4.931(0.507–47.940) 0.169 Use of Vasoactive drugs 0.785 0.384 4.179 2.193(1.033–4.658) 0.041 Sepsis 0.486 0.521 0.870 1.626(0.585–4.517) 0.351 Blood transfusion for anemia -0.375 0.419 0.802 0.687(0.303–1.561) 0.370 Discussion In this research, 205 ELBWIs were included. The frequency of PIVH occurrence was 40%, with severe PIVH observed in 12.7% of patients. Multivariate logistic regression analysis revealed that failure to withdraw IMV within 1 week of birth (OR = 3.668, 95% CI = 1.557–8.641, p = 0.003), along with the use of vasoactive drugs (OR = 2.193, 95% CI = 1.033–4.658, p = 0.041), were identified as significant independent risk factors for PIVH. An AUC of 0.792 (95% CI 0.726–0.857) was computed, with a maximum Youden index of 0.496. The sensitivity and specificity were 68.3% and 81.3%, respectively. In 2012, the U.S. Neonatal Collaborative Network on Child Health and Human Development discovered that the prevalence of severe PIVH among premature infants delivered at 22 to 28 weeks gestation was 13.1%. Of these newborns, 36.5% (626 out of 1713) were delivered at less than 26 weeks gestation, with a severe PIVH rate reaching 22.8%[ 15 ]. Bolisetty et al. [ 16 ]conducted a multicenter cohort study in Australia and the United Kingdom from 1998 to 2004 involving 2414 premature babies born between 23 and 28 weeks of gestation. Among this population, 12.6% experienced severe PIVH, with 26.8% (647 out of 2414) occurring in infants born at 26 weeks or younger. A multicenter investigation encompassing 25 NICUs in China revealed that among 8835 very low birth weight infants (VLBWIs) and ELBWIs, the prevalence of severe PIVH was 7.4%. Specifically, severe PIVH rates in infants with ELBWIs and gestational ages equal to or less than 28 weeks were 13.5% and 13.1%, respectively, and the incidence of severe PIVH in infants who delivered at less than 26 weeks gestation was 25.2%[ 17 ]. In our research, the frequency of PIVH in the ELBWI was 40%, while the rate of severe PIVH was 12.7%. Kaiser et al.[ 18 ] reported that the occurrence of severe PIVH decreased by 19% for each additional week of gestation in the ELBWIs. Our study revealed a negative relationship between gestational age and the development and severity of PIVH, suggesting that lower gestational age is linked to higher rates and increased severity of intracranial bleeding. The extended use of invasive ventilator support in preterm infants may increase the chances of PIVH[ 19 ]. Mechanical ventilation can cause changes in lung air flow and blood gas levels, which can in turn affect blood flow in the brain, potentially leading to vessel rupture and bleeding[ 20 , 21 ]. Providing CPAP and PS assistance early during delivery has been proven to lessen the need for postnatal intubation[ 22 – 24 ]. Our research showed that infants who are unable to withdraw invasive ventilation within 1 week of birth are at a 3.668 times greater risk of developing PIVH than are those who on noninvasive ventilation. Therefore, optimizing respiratory support approaches, such as early CPAP and PS therapy, is crucial for extremely low birth weight infants during the first week after birth. Promptly extubating infants who no longer require invasive ventilation can help minimize the risk of PIVH. Early administration of vasoactive drugs to premature infants can increase the risk of PIVH[ 17 , 25 ]. The excessive and prompt use of vasoactive drugs for hypotension management does not enhance outcomes in extremely premature infants and may result in sudden changes in cerebral blood flow, heightening the chances of PIVH[ 26 ]. A study conducted by Zaveri et al.[ 27 ] reported that severe PIVH occurred in 18.8% of extremely premature infants who were given vasoactive drugs within the initial week after birth, in contrast to only 2% of untreated infants. Similarly, Dempsey et al. [ 28 ] reported that ELBWIs with low blood pressure but no evidence of poor perfusion commonly exhibit natural improvements in blood pressure within 24 hours post birth, with outcomes comparable to those of normotensive infants. Our research further supported these findings by demonstrating that the administration of vasoactive drugs during the first week after birth significantly increases the risk of PIVH in ELBWIs. The likelihood of PIVH is 2.193 times greater when vasoactive drugs are used in the initial week after birth. Hence, it is imperative to exercise caution when administering vasoactive drugs in the early postnatal period for ELBWIs, which rely on a thorough assessment of blood pressure and tissue perfusion indicators to avoid excessive use and blood pressure fluctuations. This research has several limitations that should be considered. It is crucial to acknowledge that this is a retrospective study conducted at a single center with a limited number of participants. In addition, potential biases, such as confounding and temporal biases, could have impacted the outcomes of our analysis as a result of the retrospective design of the study. To improve the accuracy of the findings, it is advisable to conduct future studies at multiple centers with larger sample sizes. The prevalence of PIVH in the ELBWI is notably high, often occurring within the first three days following birth. It is essential to optimize strategies for providing respiratory support during the initial week after delivery, reduce the dependence on invasive ventilators, and use vasoactive medications carefully to prevent significant fluctuations in blood pressure. These actions are of considerable clinical importance in reducing the occurrence of PIVH in ELBWIs. Declarations Author contributions Li-XL and Song-YY proposed the idea and planned the research, oversaw and managed the data collection, revised the original manuscript, and agreed to the final version submitted. Cai-YJ and Jiang-YJ created the data collection tools, recruited patients, gathered the data, conducted the data analysis, wrote the first draft, and approved the final manuscript. Wang-P, Zhao-XP: gathered the data and approved the final manuscript. Funding This study was supported by funds from the Guangzhou Health Science and Technology Project (No.20241 A011025) Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate The study was approved by the Ethics Committee of Women and Children Medical Center Affiliated with Guangzhou Medical University (No. 350B00) in accordance with ethical guidelines. Informed consent was not required for this retrospective study, which was approved by the Ethics Committee. Consent for publication Not applicable. Competing interests The authors declare that they have no potential conflicts of interest. 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Ceylan A, Gezer S, Demir N, Tuncer O, Peker E, Kırımi E. The importance of administration of early surfactant and nasal continuous positive airway pressure in newborns with respiratory distress syndrome. Turk pediatr arsivi. 2014;49(3):192–7. Joris N, Sudre P, Moessinger A. [Early application of CPAP in newborns with gestational age below 34 weeks lowers intubation rate and shortens oxygen therapy without altering mortality and morbidity]. Schweiz med wschr. 2000;130(49):1887–93. Keerthan R, Nagaseshu P, Gopalan G, Kachroo K, Sharma J. A systematic review, meta-analysis and economic evaluation on Neonatal cpap. Comput Math Biophys. 2022;10(1):68–86. Abdul Aziz AN, Thomas S, Murthy P, Rabi Y, Soraisham A, Stritzke A, Kamaluddeen M, Al-Awad E, Mohammad K. Early inotropes use is associated with higher risk of death and/or severe brain injury in extremely premature infants. J matern-fetal neo m. 2020;33(16):2751–8. St Peter D, Gandy C, Hoffman SB. Hypotension and Adverse Outcomes in Prematurity: Comparing Definitions. Neonatology. 2017;111(3):228–33. Zaveri PG, Walker AM, Upadhyay K, Talati AJ. Use of Vasopressors in Extremely Preterm Infants in First Week of Life. Am j perinat. 2023;40(5):513–8. Dempsey EM, Al Hazzani F, Barrington KJ. Permissive hypotension in the extremely low birthweight infant with signs of good perfusion. Arch dis child-fetal 2009, 94(4):F241-244. 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 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-4286126","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":294794147,"identity":"0352c65f-5de1-4ebb-87f6-c4155dfbcb23","order_by":0,"name":"Yueju Cai","email":"","orcid":"","institution":"Guangzhou Wowen and Children's Medical Center, Guangzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yueju","middleName":"","lastName":"Cai","suffix":""},{"id":294794149,"identity":"d4b04571-b4ae-4616-bf4d-948299cf1e29","order_by":1,"name":"Yongjiang Jiang","email":"","orcid":"","institution":"Guangzhou Wowen and Children's Medical Center, Liuzhou hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yongjiang","middleName":"","lastName":"Jiang","suffix":""},{"id":294794151,"identity":"1ebc3af9-98c8-4327-b4b8-4fc41017b75c","order_by":2,"name":"Ping Wang","email":"","orcid":"","institution":"Guangzhou Wowen and Children's Medical Center, Guangzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Wang","suffix":""},{"id":294794153,"identity":"569d2636-289c-428c-afc3-525e6878a78f","order_by":3,"name":"Xiaopeng Zhao","email":"","orcid":"","institution":"Guangzhou Wowen and Children's Medical Center, Guangzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaopeng","middleName":"","lastName":"Zhao","suffix":""},{"id":294794154,"identity":"2011340a-1cdc-40fd-87e5-b10cec34ac2b","order_by":4,"name":"Yanyan Song","email":"","orcid":"","institution":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yanyan","middleName":"","lastName":"Song","suffix":""},{"id":294794155,"identity":"ef6063e5-c6ae-462b-b06d-7a34c723bc40","order_by":5,"name":"Xiaolan Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYBACA2YGhgMMDBYMDMzMBx8kVEjIyROpRYKBgb0t2eDDGQtjwwZCWiAUUAvPGTXJmW0ViSAT8Gth5zE88KNCQt5cIodBmneeRAJjA/PDRzfwOowt4WDPGQnDnTNyDxjzbpPIY2dgMzbOwauF+cAB3jYJxg038hKSgVqKGRt42KTxa2FsOPi3TcJ+w40cg8O8cyQSGw4Q1MJ84DDQlsQNZ84YNs5sIEoLW8JhmTMSyRuOtyUzfDgmYWzYTMAv9v1njD++qbCx3XCY+fiPhJo6OXn25oeP8WnBAphJUz4KRsEoGAWjAAsAAJr8S4939hhnAAAAAElFTkSuQmCC","orcid":"","institution":"Guangzhou Women and Children's Medical Center, Guangzhou Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Xiaolan","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2024-04-18 08:12:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4286126/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4286126/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55631556,"identity":"ed7c26ae-8ea7-4f24-8e59-16000f76c544","added_by":"auto","created_at":"2024-04-30 19:44:42","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":76804,"visible":true,"origin":"","legend":"\u003cp\u003eFlow of participation for extremely low birth weight infants.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4286126/v1/74075ac788b5c90876ba386d.jpeg"},{"id":55631555,"identity":"eaf2e29e-3e1a-4a47-ab5c-fb2996cedd34","added_by":"auto","created_at":"2024-04-30 19:44:42","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":43229,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve of the predictive model for PIVH\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-4286126/v1/d03205ca0447b790b0e19172.png"},{"id":55924685,"identity":"14218098-41c4-4b5a-98dc-8b0bf60bf40b","added_by":"auto","created_at":"2024-05-06 11:02:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":719470,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4286126/v1/5d0116ba-1b4c-4a3b-8a68-ddffad274e78.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Risk factors for early periventricular intraventricular hemorrhage in extremely low birth weight infants: a retrospective study","fulltext":[{"header":"Background","content":"\u003cp\u003eExtremely low birth weight infants (ELBWIs) are those who weigh less than 1000 g at birth. With advancements and progress in perinatal medicine, there has been a significant increase in the survival rate of premature infants, particularly ELBWIs[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Periventricular intraventricular hemorrhage (PIVH) is a common complication in premature infants, with a higher incidence and severity observed in those born at earlier gestational ages[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. ELBWIs have underdeveloped organs and are prone to unstable conditions, making them highly vulnerable to PIVH, which often presents with subtle, challenging-to-detect symptoms early on. PIVH can lead to developmental delays, cognitive impairments, epilepsy, disabilities, and even death, significantly impacting parents' treatment decisions and the long-term quality of life of children[\u003cspan additionalcitationids=\"CR4 CR5 CR6\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The pathogenesis of PIVH is multifaceted, with few available treatment options and a poor prognosis. PIVH typically peaks during the first week after birth, particularly within the first 3 days[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Despite several studies on the risk factors for PIVH in premature infants[\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], research on the early prediction and risk factors for early-stage PIVH in ELBWIs is scarce, posing challenges to their prevention and management.\u003c/p\u003e \u003cp\u003eOur study was a retrospective analysis of data from ELBWIs admitted to our institution. The objective was to identify risk factors for PIVH in the early stages of life among ELBWIs. The purpose of this study is to provide recommendations for implementing timely interventions to increase the survival rate and quality of life of ELBWIs.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e \u003cb\u003ePatients\u003c/b\u003e \u003c/p\u003e \u003cp\u003eA retrospective study of ELBWIs admitted to the Women and Children's Medical Center of Guangzhou Medical University from January 2019 to December 2023 was conducted. The inclusion criteria were as follows: 1) admission to the NICU within 24 hours after birth, 2) birth weight\u0026thinsp;\u0026lt;\u0026thinsp;1000 g, and 3) head ultrasound (HUS) performed on days 1\u0026ndash;3 and 5\u0026ndash;7 postbirth. Premature infants with structural organ abnormalities, congenital metabolic diseases, and chromosomal abnormalities and those who died or were discharged within 7 days after birth were excluded. Based on the HUS results, the subjects were categorized into the PIVH group and the non-PIVH group (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The study was approved by the Ethics Committee of Women and Children Medical Center Affiliated with Guangzhou Medical University (No. 350B00) in accordance with ethical guidelines. Informed consent was not required for this retrospective study, which was approved by the Ethics Committee.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eDelivery room management for premature infants\u003c/h3\u003e\n\u003cp\u003e Prior to the delivery of premature infants, pediatricians and obstetricians collaborate to develop treatment plans, engage in discussions with family members regarding the infants' condition, and obtain informed consent. The pediatric team is present in the delivery room before birth and is ready for use with preresuscitation equipment. Immediately after birth, it is crucial to ensure that premature infants are kept warm, their airways are cleared of secretions, and they are provided with CPAP support. Once stabilized, the infant is promptly transferred to the NICU for ongoing monitoring and treatment. Pulmonary surfactant (PS) is administered in the NICU via MIST. Infants not requiring tracheal intubation receive noninvasive respiratory support.\u003c/p\u003e\n\u003ch3\u003eUltrasound\u003c/h3\u003e\n\u003cp\u003eSkilled attending physicians in the ultrasound department utilized the Philips Epiq5 color Doppler ultrasound system (Philips Ultrasound, Inc., Washington, USA) to perform HUS exams on newborns on days 1\u0026ndash;3 and 5\u0026ndash;7 postbirth. The severity of the PIVH was assessed based on the Papile system. PIVH is divided into four grades according to the PIVH diagnosis and Papile classification criteria: Grade I - subependymal hemorrhage; Grade II - intraventricular hemorrhage, covering 10\u0026ndash;50% of the area; Grade III - intraventricular hemorrhage with ventricular enlargement, bleeding area exceeding 50%; Grade IV - intraventricular hemorrhage with ventricular enlargement and cerebral parenchymal hemorrhage. Grades I and II are considered mild, while grades III and IV are categorized as severe PIVH.\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eThe medical records of the infants were reviewed during hospitalization to document important information such as sex, gestational age, birth weight, mode of delivery, place of delivery, IVF status, presence of twins, premature rupture of membranes, characteristics of amniotic fluid, use of prenatal glucocorticoids, and magnesium sulfate. Maternal complications such as gestational diabetes and hypertension, intrauterine distress, intrauterine infection, threatened preterm labor, resuscitation measures during delivery (including resuscitation for asphyxiation, endotracheal intubation, chest compressions, and pure oxygen resuscitation), 1-minute and 5-minute Apgar scores, failure to withdraw invasive ventilators within 1 week, use of high frequency oscillatory ventilation (HFOV) for at least 24 hours, administration of vasoactive drugs, nitric oxide (NO), and PS treatment, occurrence of sepsis, presence of PDA and treatment with ibuprofen, anemia and blood transfusion status, and presence of coagulation disorders and thrombocytopenia were also documented.\u003c/p\u003e\n\u003ch3\u003eStatistical methods\u003c/h3\u003e\n\u003cp\u003eSPSS software, version 25.0 from IBM Corp. in Armonk, NY, was utilized for performing the statistical analysis. The presentation of the data varied depending on their distribution, with the mean and standard deviation or median and interquartile range (IQR) being used. The frequency data are presented as numbers (n) and percentages (%). Group differences were evaluated using the independent sample t test for normally distributed variables and the Mann\u0026ndash;Whitney U test for nonnormally distributed variables. Categorical variables were analyzed using the chi-square test. The risks associated with PIVH were determined through logistic regression analysis. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the model. An area under the curve (AUC) greater than 0.75 indicates high discrimination. The Hosmer‒Lemeshow test was used to calibrate the model. The significance level was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, which suggests a good model fit with no significant difference between the predicted and true values.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cb\u003eDemographic characteristics of the ELBWI in the PIVH and non-PIVH groups\u003c/b\u003e \u003c/p\u003e \u003cp\u003eA total of 205 ELBWIs, including 97 males and 108 females, were included in this study, with a male to female ratio of 0.90:1. Among them, 190 patients (92.7%) were born at our hospital, and 15 patients (7.3%) were born at other hospitals. The mean gestational age of the ELBWIs was 27.3 (26.5, 28.6) weeks, and the mean birth weight was 870 (750, 950) grams. There were 82 cases (40%) of PIVH, of which 51 cases (62.2%) occurred within 3 days after birth and 31 cases (37.8%) occurred within 4 to 7 days after birth. Among the 205 ELBWIs, 26 (12.6%) had severe PIVH, and 56 (27.3%) had mild PIVH. The incidence rates of PIVH in the 23\u003csup\u003e+\u0026thinsp;1\u003c/sup\u003e-26-, 26\u003csup\u003e+\u0026thinsp;1\u003c/sup\u003e-28-, and 28\u003csup\u003e+\u0026thinsp;1\u003c/sup\u003e-32-week groups were 72.5% (29/40), 33.3% (31/93), and 30.6% (22/72), respectively, and the difference was statistically significant (χ2\u0026thinsp;=\u0026thinsp;22.002, p\u0026thinsp;=\u0026thinsp;0.000). The incidence rates of severe PIVH in the 23\u003csup\u003e+\u0026thinsp;1\u003c/sup\u003e-26-, 26\u003csup\u003e+\u0026thinsp;1\u003c/sup\u003e-28-, and 28\u003csup\u003e+\u0026thinsp;1\u003c/sup\u003e-32-week groups were 40.0% (16/40), 10.7% (10/93), and 1.4% (1/72), respectively, and the difference was statistically significant (χ2\u0026thinsp;=\u0026thinsp;34.392, p\u0026thinsp;=\u0026thinsp;0.000).\u003c/p\u003e \u003cp\u003eCompared to the non-PIVH group, the PIVH group had a significantly younger gestational age and lower birth weight (p\u0026thinsp;=\u0026thinsp;0.000 and p\u0026thinsp;=\u0026thinsp;0.021, respectively). In the PIVH group, 59.8% of infants were delivered by cesarean section, while in the non-PIVH group, this percentage was 28.5% (p\u0026thinsp;=\u0026thinsp;0.000). Additionally, 56.1% (46/82) of infants in the PIVH group required resuscitation at birth (p\u0026thinsp;=\u0026thinsp;0.003), and 47.6% (39/82) needed endotracheal intubation in the delivery room (p\u0026thinsp;=\u0026thinsp;0.001). The median 1-minute Apgar score was 7 (5,8) in the PIVH group and 8 (6,8) in the non-PIVH group (p\u0026thinsp;=\u0026thinsp;0.003). No significant differences in sex, place of delivery, IVF status, presence of twins, premature rupture of membranes, presence of amniotic fluid, fetal distress, 5-minute Apgar score, chest compressions in the delivery room, threatened preterm labor, antenatal use of glucocorticoids, antenatal use of MgSO4, intrauterine infection, gestational diabetes mellitus or gestational hypertension were found between the PIVH group and the non-PIVH group (all 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\u003eDemographic characteristics of extremely low birth weight infants in PIVH and non-PIVH groups\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=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \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\u003eValues\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePIVH(n\u0026thinsp;=\u0026thinsp;82)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-PIVH(n\u0026thinsp;=\u0026thinsp;123)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ2/Z\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41(50.0)\u003c/p\u003e \u003cp\u003e41(50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56(45.5)\u003c/p\u003e \u003cp\u003e67(54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.395\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.530\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27(25.6,28.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.5(27,29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;4.100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e835(700,940)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e890(780,950)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;2.312\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMode of delivery\u003c/p\u003e \u003cp\u003eVaginal delivery\u003c/p\u003e \u003cp\u003eCesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33(40.2)\u003c/p\u003e \u003cp\u003e49(59.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88(71.5)\u003c/p\u003e \u003cp\u003e35(28.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.931\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelivery site\u003c/p\u003e \u003cp\u003eIn-born\u003c/p\u003e \u003cp\u003eOut-born\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74(90.2)\u003c/p\u003e \u003cp\u003e8 (9.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116(94.3)\u003c/p\u003e \u003cp\u003e7(5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.199\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.274\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple pregnancy\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25(30.5)\u003c/p\u003e \u003cp\u003e57(69.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39(31.7)\u003c/p\u003e \u003cp\u003e84(68.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.854\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVF\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(23.2)\u003c/p\u003e \u003cp\u003e63(76.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(17.1)\u003c/p\u003e \u003cp\u003e102(82.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.165\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.280\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePremature rupture of membranes\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(19.5)\u003c/p\u003e \u003cp\u003e66(80.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38(30.9)\u003c/p\u003e \u003cp\u003e85(69.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStained amniotic fluid\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(12.2)\u003c/p\u003e \u003cp\u003e72(87.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17(13.8)\u003c/p\u003e \u003cp\u003e106(86.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.736\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFetal distress\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(17.1)\u003c/p\u003e \u003cp\u003e68(82.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(15.4)\u003c/p\u003e \u003cp\u003e104(84.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.096\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.756\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResuscitation at birth\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46(56.1)\u003c/p\u003e \u003cp\u003e36(43.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43(35.0)\u003c/p\u003e \u003cp\u003e80(65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.949\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApgar score\u003c/p\u003e \u003cp\u003e1- minute\u003c/p\u003e \u003cp\u003e5- minute\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(5,8)\u003c/p\u003e \u003cp\u003e8(8,9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(6,8)\u003c/p\u003e \u003cp\u003e9(8,9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;2.954\u003c/p\u003e \u003cp\u003e\u0026minus;1.437\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChest compressions in delivery room\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(6.1)\u003c/p\u003e \u003cp\u003e77(93.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(5.7)\u003c/p\u003e \u003cp\u003e116(94.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntubated in delivery room\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39(47.6)\u003c/p\u003e \u003cp\u003e43(52.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32(26.0)\u003c/p\u003e \u003cp\u003e91(74.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.088\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThreatened preterm labor\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56(68.3)\u003c/p\u003e \u003cp\u003e26(31.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78(63.4)\u003c/p\u003e \u003cp\u003e45(36.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.517\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.472\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntenatal use of glucocorticoids\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47(57.3)\u003c/p\u003e \u003cp\u003e35(42.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84(68.3)\u003c/p\u003e \u003cp\u003e39(31.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.569\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.109\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntenatal use of MgSO4\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38(46.3)\u003c/p\u003e \u003cp\u003e44(53.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67(54.5)\u003c/p\u003e \u003cp\u003e56(45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.302\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.254\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntrauterine infection\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(9.8)\u003c/p\u003e \u003cp\u003e74(90.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(8.1)\u003c/p\u003e \u003cp\u003e113(91.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.687\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational diabetes mellitus\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(15.9)\u003c/p\u003e \u003cp\u003e69(84.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(16.3)\u003c/p\u003e \u003cp\u003e103(83.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.938\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational hypertension\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(19.5)\u003c/p\u003e \u003cp\u003e66(80.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38(30.9)\u003c/p\u003e \u003cp\u003e85(69.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eTreatments and Complications of the ELBWI in the PIVH and Non-PIVH Groups\u003c/h3\u003e\n\u003cp\u003eCompared to the non-PIVH group, the PIVH group had a greater percentage of infants who could not be weaned off the ventilator within 1 week of birth (73.0% vs. 30.1%, p\u0026thinsp;=\u0026thinsp;0.000). Moreover, a larger proportion of infants in the PIVH group needed high-frequency ventilators for more than 24 hours (34.1% vs. 8.1%, p\u0026thinsp;=\u0026thinsp;0.000), as well as nitric oxide (13.4% vs. 0.8%, p\u0026thinsp;=\u0026thinsp;0.001) and vasoactive drugs (50.0% vs. 18.7%, p\u0026thinsp;=\u0026thinsp;0.000). The incidence of sepsis and the requirement for blood transfusions to address anemia were also greater in the PIVH group (28.0% vs. 8.9%, p\u0026thinsp;=\u0026thinsp;0.000, and 48.8% vs. 26.0%, p\u0026thinsp;=\u0026thinsp;0.001, respectively). Nevertheless, there were no significant differences in the occurrence of PS use, PDA, anemia, coagulation disorders, or thrombocytopenia between the two groups. (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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\u003e Treatments and Complications of ELBWI in PIVH and Non-PIVH groups\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=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \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\u003eValues\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePIVH(n\u0026thinsp;=\u0026thinsp;82)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-PIVH(n\u0026thinsp;=\u0026thinsp;123)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFailure to withdraw IMV\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60(73.2)\u003c/p\u003e \u003cp\u003e22(26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37(30.1)\u003c/p\u003e \u003cp\u003e86(69.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e36.645\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of HFOV for at least 24 hours\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28(34.1)\u003c/p\u003e \u003cp\u003e54(65.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(8.1)\u003c/p\u003e \u003cp\u003e113(91.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22.053\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of NO\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(13.4)\u003c/p\u003e \u003cp\u003e71(86.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.8)\u003c/p\u003e \u003cp\u003e122(99.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11.983\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of PS\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71(86.6)\u003c/p\u003e \u003cp\u003e11(13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96(78.0)\u003c/p\u003e \u003cp\u003e27(22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.374\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.123\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of Vasoactive drugs\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41(50.0)\u003c/p\u003e \u003cp\u003e41(50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(18.7)\u003c/p\u003e \u003cp\u003e100(81.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22.448\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepsis\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23(28.0)\u003c/p\u003e \u003cp\u003e59(72.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(8.9)\u003c/p\u003e \u003cp\u003e112(91.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.981\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePDA\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53(64.6)\u003c/p\u003e \u003cp\u003e29(35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67(54.5)\u003c/p\u003e \u003cp\u003e56(45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.094\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.148\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIbuprofen treatment for PDA\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.4)\u003c/p\u003e \u003cp\u003e80(97.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (5.7)\u003c/p\u003e \u003cp\u003e116(94.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.586\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.444\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnemia\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64(78.0)\u003c/p\u003e \u003cp\u003e18(22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81(65.9)\u003c/p\u003e \u003cp\u003e42(34.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.534\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.060\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood transfusion for anemia\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40(48.8)\u003c/p\u003e \u003cp\u003e42(51.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32(26.0)\u003c/p\u003e \u003cp\u003e91(74.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11.189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoagulation dysfunction\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(12.2)\u003c/p\u003e \u003cp\u003e13(15.9)\u003c/p\u003e \u003cp\u003e59(72.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (6.5)\u003c/p\u003e \u003cp\u003e28(22.8)\u003c/p\u003e \u003cp\u003e87(70.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.223\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombopenia\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50(61.0)\u003c/p\u003e \u003cp\u003e32(39.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72(58.5)\u003c/p\u003e \u003cp\u003e51(41.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.727\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eIMV: invasive mechanical ventilation, HFOV: high frequency oscillatory ventilation, NO: nitric oxide, PS: pulmonary surfactant, PDA: patent ductus arteriosus\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eRisk factors and prediction for PIVH in the ELBWI\u003c/h3\u003e\n\u003cp\u003eThe studies included significant risk factors in the univariate analysis, such as gestational age, birth weight, mode of delivery, resuscitation at birth, 1-minute Apgar score, intubation in the delivery room, failure to withdraw IMV within 1 week of birth, use of HFO for at least 24 hours, use of NO, use of vasoactive drugs, sepsis, and blood transfusion for anemia. According to the multivariable logistic regression analysis, failure to withdraw IMV within 1 week of birth (OR\u0026thinsp;=\u0026thinsp;3.668, 95% CI\u0026thinsp;=\u0026thinsp;1.557\u0026ndash;8.641; P\u0026thinsp;=\u0026thinsp;0.003) and the use of vasoactive drugs (OR\u0026thinsp;=\u0026thinsp;2.193, 95% CI\u0026thinsp;=\u0026thinsp;1.033\u0026ndash;4.658; P\u0026thinsp;=\u0026thinsp;0.041) were identified as independent risk factors for PIVH, as detailed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Analysis of the ROC curve demonstrated that the model achieved an AUC of 0.792 (95% CI 0.726\u0026ndash;0.857), with a maximum Youden index of 0.496. The sensitivity and specificity were calculated to be 68.3% and 81.3%, respectively, as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The omnibus test revealed that the current model significantly outperformed the null model (χ2\u0026thinsp;=\u0026thinsp;58.304, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, the Hosmer \u0026amp; Lemeshow test (χ2\u0026thinsp;=\u0026thinsp;7.041, p\u0026thinsp;=\u0026thinsp;0.532) indicated that the model fit the data accurately.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e Analysis of risk factors for PIVH in ELBWI\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=\"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 \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\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eβ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWald χ2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR (95% CI)\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\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.702\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.890(0.678\u0026ndash;1.169)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.402\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.000\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\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000(0.997\u0026ndash;1.003)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.892\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMode of delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.978(0.430\u0026ndash;2.224)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.958\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResuscitation at birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.761\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.536\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.140(0.749\u0026ndash;6.114)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.156\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1-minute Apgar score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.178(0.888\u0026ndash;1.564)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.256\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntubated in delivery room\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.445\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.228\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.237(0.517\u0026ndash;2.962)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.633\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFailure to withdraw IMV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.437\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.838\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.668(1.557\u0026ndash;8.641)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of HFOV for at least 24 hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.612\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.495\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.844(0.692\u0026ndash;4.916)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.221\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of NO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.890\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.931(0.507\u0026ndash;47.940)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.169\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse of Vasoactive drugs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.785\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.384\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.193(1.033\u0026ndash;4.658)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.486\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.521\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.870\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.626(0.585\u0026ndash;4.517)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.351\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood transfusion for anemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.375\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.802\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.687(0.303\u0026ndash;1.561)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.370\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this research, 205 ELBWIs were included. The frequency of PIVH occurrence was 40%, with severe PIVH observed in 12.7% of patients. Multivariate logistic regression analysis revealed that failure to withdraw IMV within 1 week of birth (OR\u0026thinsp;=\u0026thinsp;3.668, 95% CI\u0026thinsp;=\u0026thinsp;1.557\u0026ndash;8.641, p\u0026thinsp;=\u0026thinsp;0.003), along with the use of vasoactive drugs (OR\u0026thinsp;=\u0026thinsp;2.193, 95% CI\u0026thinsp;=\u0026thinsp;1.033\u0026ndash;4.658, p\u0026thinsp;=\u0026thinsp;0.041), were identified as significant independent risk factors for PIVH. An AUC of 0.792 (95% CI 0.726\u0026ndash;0.857) was computed, with a maximum Youden index of 0.496. The sensitivity and specificity were 68.3% and 81.3%, respectively.\u003c/p\u003e \u003cp\u003eIn 2012, the U.S. Neonatal Collaborative Network on Child Health and Human Development discovered that the prevalence of severe PIVH among premature infants delivered at 22 to 28 weeks gestation was 13.1%. Of these newborns, 36.5% (626 out of 1713) were delivered at less than 26 weeks gestation, with a severe PIVH rate reaching 22.8%[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Bolisetty et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]conducted a multicenter cohort study in Australia and the United Kingdom from 1998 to 2004 involving 2414 premature babies born between 23 and 28 weeks of gestation. Among this population, 12.6% experienced severe PIVH, with 26.8% (647 out of 2414) occurring in infants born at 26 weeks or younger. A multicenter investigation encompassing 25 NICUs in China revealed that among 8835 very low birth weight infants (VLBWIs) and ELBWIs, the prevalence of severe PIVH was 7.4%. Specifically, severe PIVH rates in infants with ELBWIs and gestational ages equal to or less than 28 weeks were 13.5% and 13.1%, respectively, and the incidence of severe PIVH in infants who delivered at less than 26 weeks gestation was 25.2%[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In our research, the frequency of PIVH in the ELBWI was 40%, while the rate of severe PIVH was 12.7%. Kaiser et al.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] reported that the occurrence of severe PIVH decreased by 19% for each additional week of gestation in the ELBWIs. Our study revealed a negative relationship between gestational age and the development and severity of PIVH, suggesting that lower gestational age is linked to higher rates and increased severity of intracranial bleeding.\u003c/p\u003e \u003cp\u003eThe extended use of invasive ventilator support in preterm infants may increase the chances of PIVH[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Mechanical ventilation can cause changes in lung air flow and blood gas levels, which can in turn affect blood flow in the brain, potentially leading to vessel rupture and bleeding[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Providing CPAP and PS assistance early during delivery has been proven to lessen the need for postnatal intubation[\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Our research showed that infants who are unable to withdraw invasive ventilation within 1 week of birth are at a 3.668 times greater risk of developing PIVH than are those who on noninvasive ventilation. Therefore, optimizing respiratory support approaches, such as early CPAP and PS therapy, is crucial for extremely low birth weight infants during the first week after birth. Promptly extubating infants who no longer require invasive ventilation can help minimize the risk of PIVH.\u003c/p\u003e \u003cp\u003eEarly administration of vasoactive drugs to premature infants can increase the risk of PIVH[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The excessive and prompt use of vasoactive drugs for hypotension management does not enhance outcomes in extremely premature infants and may result in sudden changes in cerebral blood flow, heightening the chances of PIVH[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. A study conducted by Zaveri et al.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] reported that severe PIVH occurred in 18.8% of extremely premature infants who were given vasoactive drugs within the initial week after birth, in contrast to only 2% of untreated infants. Similarly, Dempsey et al. [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] reported that ELBWIs with low blood pressure but no evidence of poor perfusion commonly exhibit natural improvements in blood pressure within 24 hours post birth, with outcomes comparable to those of normotensive infants. Our research further supported these findings by demonstrating that the administration of vasoactive drugs during the first week after birth significantly increases the risk of PIVH in ELBWIs. The likelihood of PIVH is 2.193 times greater when vasoactive drugs are used in the initial week after birth. Hence, it is imperative to exercise caution when administering vasoactive drugs in the early postnatal period for ELBWIs, which rely on a thorough assessment of blood pressure and tissue perfusion indicators to avoid excessive use and blood pressure fluctuations.\u003c/p\u003e \u003cp\u003eThis research has several limitations that should be considered. It is crucial to acknowledge that this is a retrospective study conducted at a single center with a limited number of participants. In addition, potential biases, such as confounding and temporal biases, could have impacted the outcomes of our analysis as a result of the retrospective design of the study. To improve the accuracy of the findings, it is advisable to conduct future studies at multiple centers with larger sample sizes. The prevalence of PIVH in the ELBWI is notably high, often occurring within the first three days following birth. It is essential to optimize strategies for providing respiratory support during the initial week after delivery, reduce the dependence on invasive ventilators, and use vasoactive medications carefully to prevent significant fluctuations in blood pressure. These actions are of considerable clinical importance in reducing the occurrence of PIVH in ELBWIs.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLi-XL and Song-YY proposed the idea and planned the research, oversaw and managed the data collection, revised the original manuscript, and agreed to the final version submitted. Cai-YJ and Jiang-YJ created the data collection tools, recruited patients, gathered the data, conducted the data analysis, wrote the first draft, and approved the final manuscript. Wang-P, Zhao-XP: gathered the data and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by funds from the Guangzhou Health Science and Technology Project (No.20241\u003c/p\u003e\n\u003cp\u003eA011025)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Women and Children Medical Center Affiliated with Guangzhou Medical University (No. 350B00) in accordance with ethical guidelines. Informed consent was not required for this retrospective study, which was approved by the Ethics Committee.\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\u003eThe authors declare that they have no potential conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRamaswamy VV, Abiramalatha T, Bandyopadhyay T, Shaik NB, Bandiya P, Nanda D, Pullattayil SAK, Murki S, Roehr CC. ELBW and ELGAN outcomes in developing nations-Systematic review and meta-analysis. PLoS ONE. 2021;16(8):e0255352.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLai GY, Shlobin N, Garcia RM, Wescott A, Kulkarni AV, Drake J, Dizon ML, Lam SK. Global incidence proportion of intraventricular haemorrhage of prematurity: a meta-analysis of studies published 2010\u0026ndash;2020. \u003cem\u003eArch dis child-fetal\u003c/em\u003e 2022, 107(5):513\u0026ndash;519.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaempf JW, Guillen U, Litt JS, Zupancic JAF, Kirpalani H. Change in neurodevelopmental outcomes for extremely premature infants over time: a systematic review and meta-analysis. \u003cem\u003eArch dis child-fetal\u003c/em\u003e 2023, 108(5):458\u0026ndash;463.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePande GS, Vagha JD. A Review of the Occurrence of Intraventricular Hemorrhage in Preterm Newborns and its Future Neurodevelopmental Consequences. Cureus. 2023;15(11):e48968.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark J, Park SH, Kwon YR, Yoon SJ, Lim JH, Han JH, Shin JE, Eun HS, Park MS, Lee SM. Long-term outcomes of very low birth weight infants with intraventricular hemorrhage: a nationwide population study from 2011 to 2019. \u003cem\u003eWorld j pediatr\u003c/em\u003e 2024, null(null):null.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePascal A, de Bruyn N, Naulaers G, Ortibus E, Hanssen B, Oostra A, de Coen K, Sonnaert M, Cloet E, Casaer A et al. The Impact of Intraventricular Hemorrhage and Periventricular Leukomalacia on Mortality and Neurodevelopmental Outcome in Very Preterm and Very Low Birthweight Infants: A Prospective Population-based Cohort Study. \u003cem\u003eJ pediatr-us\u003c/em\u003e 2023, 262(null):113600.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSakaue S, Hasegawa T, Sakai K, Zen Y, Tozawa T, Chiyonobu T, Yamada K, Morimoto M, Hosoi H. Low-grade IVH in preterm infants causes cerebellar damage, motor, and cognitive impairment. Pediatr int. 2021;63(11):1327\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitrea G, Matasaru M, Ilie L, Diana-Andreea C, Filip A. Intraventricular Hemorrhage in Premature Infants: A Review of Risk Factors, Pathology, Treatment, and Prognosis. ARS Med Tomitana. 2023;29(3):191\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKadri H, Mawla AA, Kazah J. The incidence, timing, and predisposing factors of germinal matrix and intraventricular hemorrhage (GMH/IVH) in preterm neonates. Child nerv syst. 2006;22(9):1086\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaghshenas-Mojaveri M, Alikabranya Omran F, Khafri S, Mehraein R, Hejazian E, Akbarian-Rad Z. The Frequency of Intraventricular Hemorrhage and its Risk Factors. \u003cem\u003eCurr pediatr rev\u003c/em\u003e 2024, null(null):null.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePoryo M, Boeckh JC, Gortner L, Zemlin M, Duppr\u0026eacute; P, Ebrahimi-Fakhari D, Wagenpfeil S, Heckmann M, Mildenberger E, Hilgendorff A, et al. Ante-, peri- and postnatal factors associated with intraventricular hemorrhage in very premature infants. Early hum dev. 2018;116(null):1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePuerta-Mart\u0026iacute;nez AG, L\u0026oacute;pez-Garrido E, Guerrero-Nava JM, Vargas-Ruiz R, Mart\u0026iacute;nez-Padr\u0026oacute;n HY. Risk factors associated with intraventricular hemorrhage in very-low-birth-weight premature infants. \u003cem\u003eChild nerv syst\u003c/em\u003e 2024, null(null):null.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXing S, Sun HQ, Li MC. [Clinical characteristics and risk factors of periventricular-intraventricular hemorrhage in extremely low birth weight infants]. Zhonghua Yi Xue Za Zhi. 2022;102(47):3774\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao Y, Zhang W, Tian X. Analysis of risk factors of early intraventricular hemorrhage in very-low-birth-weight premature infants: a single center retrospective study. BMC Pregnancy Childbirth. 2022;22(1):890.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, Laptook AR, S\u0026aacute;nchez PJ, Van Meurs KP, Wyckoff M, et al. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993\u0026ndash;2012. Jama-j am med assoc. 2015;314(10):1039\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBolisetty S, Dhawan A, Abdel-Latif M, Bajuk B, Stack J, Lui K. Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Pediatrics. 2014;133(1):55\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGroup RoIiCNICUUtE-bPfIQS. [Incidence and risk factors of severe intraventricular hemorrhage in very low and extremely low birth weight infants: a multi-center study]. Zhonghua Er Ke Za Zhi. 2019;57(4):258\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaiser JR, Gauss CH, Pont MM, Williams DK. Hypercapnia during the first 3 days of life is associated with severe intraventricular hemorrhage in very low birth weight infants. J perinatol. 2006;26(5):279\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSauer CW, Kong JY, Vaucher YE, Finer N, Proudfoot JA, Boutin MA, Leone TA. Intubation Attempts Increase the Risk for Severe Intraventricular Hemorrhage in Preterm Infants-A Retrospective Cohort Study. J pediatr-us. 2016;177(null):108\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown MK, Poeltler DM, Hassen KO, Lazarus DV, Brown VK, Stout JJ, Rich WD, Katheria AC. Incidence of Hypocapnia, Hypercapnia, and Acidosis and the Associated Risk of Adverse Events in Preterm Neonates. Resp care. 2018;63(8):943\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePiatek M, Jawdeh EGA, Giannone P, Miller B, Schadler A, Hanna M. Severe Intraventricular Hemorrhage is Associated with Lung Injury in Preterm Infants on Mechanical Ventilation. J Pediatr Perinatol Child Health. 2023;7(4):229\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCeylan A, Gezer S, Demir N, Tuncer O, Peker E, Kırımi E. The importance of administration of early surfactant and nasal continuous positive airway pressure in newborns with respiratory distress syndrome. Turk pediatr arsivi. 2014;49(3):192\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJoris N, Sudre P, Moessinger A. [Early application of CPAP in newborns with gestational age below 34 weeks lowers intubation rate and shortens oxygen therapy without altering mortality and morbidity]. Schweiz med wschr. 2000;130(49):1887\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeerthan R, Nagaseshu P, Gopalan G, Kachroo K, Sharma J. A systematic review, meta-analysis and economic evaluation on Neonatal cpap. Comput Math Biophys. 2022;10(1):68\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbdul Aziz AN, Thomas S, Murthy P, Rabi Y, Soraisham A, Stritzke A, Kamaluddeen M, Al-Awad E, Mohammad K. Early inotropes use is associated with higher risk of death and/or severe brain injury in extremely premature infants. J matern-fetal neo m. 2020;33(16):2751\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSt Peter D, Gandy C, Hoffman SB. Hypotension and Adverse Outcomes in Prematurity: Comparing Definitions. Neonatology. 2017;111(3):228\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZaveri PG, Walker AM, Upadhyay K, Talati AJ. Use of Vasopressors in Extremely Preterm Infants in First Week of Life. Am j perinat. 2023;40(5):513\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDempsey EM, Al Hazzani F, Barrington KJ. Permissive hypotension in the extremely low birthweight infant with signs of good perfusion. \u003cem\u003eArch dis child-fetal\u003c/em\u003e 2009, 94(4):F241-244.\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":"Risk factors, Periventricular hemorrhage, Extremely low birth weight infants, Incidence, Preterm","lastPublishedDoi":"10.21203/rs.3.rs-4286126/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4286126/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThis study aimed to explore the risk factors for early periventricular intraventricular hemorrhage (PIVH) in extremely low birth weight infants (ELBWIs), provide guidance for early intervention, and improve the survival rate and life expectancy of ELBWIs.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective study was conducted on 205 ELBWIs admitted to the Women and Children's Medical Center of Guangzhou Medical University from January 2019 to December 2023. The presence and severity of PIVH were assessed through standard head ultrasound screening (HUS) using the modified Papile classification on days 1\u0026ndash;3 and 5\u0026ndash;7 postbirth. The infants were categorized into either the PIVH group or the non-PIVH group based on the HUS findings. Univariate analysis and logistic regression were employed to identify the risk factors associated with PIVH. The efficacy of the model was evaluated using a receiver operating characteristic (ROC) curve.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong the 205 ELBWIs (97 males and 108 females) included in the study, 82 patients (40.0%) developed PIVH, 26 patients (12.7%) had severe PIVH, and 56 patients (27.3%) had mild PIVH. Of the 82 PIVH cases, 51 occurred within 3 days after birth. The incidence rates of severe PIVH in the 23\u003csup\u003e+\u0026thinsp;1\u003c/sup\u003e-26-, 26\u003csup\u003e+\u0026thinsp;1\u003c/sup\u003e-28-, and 28\u003csup\u003e+\u0026thinsp;1\u003c/sup\u003e-32-week gestational age groups were 40.0% (16/40), 10.7% (10/93), and 1.4% (1/72), respectively (χ2\u0026thinsp;=\u0026thinsp;34.392, p\u0026thinsp;=\u0026thinsp;0.000). Logistic regression analysis revealed that failure to withdraw invasive ventilators within 1 week (OR\u0026thinsp;=\u0026thinsp;3.668, 95% CI\u0026thinsp;=\u0026thinsp;1.557\u0026ndash;8.641, p\u0026thinsp;=\u0026thinsp;0.003) and the use of vasoactive drugs within 1 week (OR\u0026thinsp;=\u0026thinsp;2.193, 95% CI\u0026thinsp;=\u0026thinsp;1.033\u0026ndash;4.658, p\u0026thinsp;=\u0026thinsp;0.041) were independent risk factors for PIVH (sensitivity\u0026thinsp;=\u0026thinsp;68.3%).The specificity was 81.3%, and the AUC was 0.792.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe incidence of PIVH in extremely low birth weight infants is relatively high, particularly within the first three days after birth. The use of vasoactive drugs and delayed removal of invasive ventilators may increase the risk.\u003c/p\u003e","manuscriptTitle":"Risk factors for early periventricular intraventricular hemorrhage in extremely low birth weight infants: a retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-30 19:44:38","doi":"10.21203/rs.3.rs-4286126/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":"2ae4ffe9-0cd7-4168-9650-b550d406b32d","owner":[],"postedDate":"April 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-06T10:54:32+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-30 19:44:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4286126","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4286126","identity":"rs-4286126","version":["v1"]},"buildId":"omnImTCwR2MFx8CMYfrG7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}