Short-term outcomes and predictive factors of mortality among Very Low Birth Weight newborns (< 1500g): cross-sectional study in the Neonatal Intensive Care Unit of Monastir, Tunisia.

Short-term outcomes and predictive factors of mortality among Very Low Birth Weight newborns (< 1500g): cross-sectional study in the Neonatal Intensive Care Unit of Monastir, Tunisia. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Short-term outcomes and predictive factors of mortality among Very Low Birth Weight newborns (< 1500g): cross-sectional study in the Neonatal Intensive Care Unit of Monastir, Tunisia. Maroua El Ouaer, Siwar Abdelmoula, Rania Naffeti, Hayet Ben Hamida, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7754946/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 13 You are reading this latest preprint version Abstract Background Although the continuous progress of medical care, Very Low Birth Weight (VLBW) infants still have a high risk of mortality and encounter many morbidities, especially in developing countries. This study aimed to describe mortality and morbidity rates and to identify predictive factors of mortality among VLBW neonates. Methods We conducted an exhaustive cross-sectional study in the neonatal Intensive Care Unit of the Teaching Hospital of Monastir in Tunisia, from January 2019 to December 2022. All VLBW infants were included except those with lethal malformations or who died in the delivery room. Data were retrospectively collected and analyzed using SPSS version 21. Results A total of 253 neonates were included with a prevalence of 1.2% among live births. Median gestational age was 30 weeks [25–37 weeks], and median birth weight was 1280g [685-1490g]. Mortality rate was 13.8%, with a median age at death of 6 days. Main causes of death were nosocomial infections (38.2%), Respiratory Distress Syndrome (20.6%), and perinatal asphyxia (17.7%). Independent predictor factors of mortality included birth weight < 1000g, seizure, catheter-related complications, and mechanical ventilation. Non-invasive ventilation was protective. All neonates born more than 32 weeks survived. Conclusion Mortality among VLBW infants remains high. Preventing infections, reducing catheter complications, and promoting non-invasive ventilation are key strategies to improve outcomes. Infant Very Low Birth Weight - Mortality – Morbidity-Survival Figures Figure 1 1. Introduction VLBW infants are defined as newborns with a body weight of less than 1500 grams at birth (1). Premature birth, including VLBW, is the leading cause of infant mortality worldwide, with an estimated 28% of global neonatal deaths directly attributable to it (2). Despite the improvement of the management in neonatal intensive care units, VLBW infants still have a high rate of mortalities and record morbidities, especially in developing countries (1,3). Common complications include Respiratory Distress Syndrome, Patent Ductus Arteriosus, sepsis, necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, and retinopathy of prematurity. These conditions prolong hospitalization and increase healthcare costs (4). Additionally, late-onset sepsis remains a major concern in VLBW infant care (5). Therefore, understanding the predictive factors of mortality, evolving clinical practices, and neonatal outcomes in VLBW infants is crucial for improving their future health. Studying these trends and identifying disparities in outcomes and care practices allows the development of targeted strategies to minimize adverse outcomes and optimize care for these vulnerable newborns. The aims of this study are to describe the rate of mortality and morbidity among VLBW neonates and also to identify predictive factors of mortality. 2. Methods 2.1. Study design and setting : We conducted a cross-sectional study in the Neonatal Intensive Care Unit of the Teaching Hospital Fattouma Bourguiba in Monastir, which serves the central and southern regions of Tunisia. This unit is a third level unit, and one of the six units of Tunisia. The period of the study is four years, from january 2019 to december 2022. 2.2. Participants : We included all newborns with VLBW (less than 1500g) regardless of gestational age. We excluded VLBW infants with chromosomal abnormalities, congenital heart defects, and other malformations incompatible with life. Infants who died in the delivery room were not included. 2.3. Study size : This was an exhaustive study including all VLBW newborns meeting the inclusion and exclusion criteria throughout the study period. 2.4. Variables : Data was collected retrospectively from medical records using a pre-established collection form. Variables extracted included antenatal care, corticosteroid use, gestational age, birth weight, ventilation use, and enteral nutrition. Mortality was defined as death before discharge from the hospital. The following morbidities were releaved : Respiratory Distress Syndrome (RDS) based on clinical findings and chest X-ray radiography, Intra-Ventricular Hemorrhage (IVH) diagnosed by brain ultrasonography, Persistent Ductus Arteriosus (PDA) confirmed by echocardiography realized by a neonatologist or cardiopediatrician, Necrotising Enterocolitis (NEC) diagnosed by radiography and clinical symptoms, Nosocomial infection confirmed by blood culture and based on clinical symptoms and Broncho-Pulmonary Dysplasia (BPD) defined as the need for supplemental oxygen at 36 weeks' postmenstrual age. 2.5. Statistical methods: Statistical analysis was performed using SPSS (Statistical Package for the Social Sciences) version 21. Qualitative variables were described by counts and percentages. Quantitative variables were assessed for distribution using the Kolmogorov-Smirnov test. Variables following a normal distribution were reported as means and standard deviations, while those not following a normal distribution were reported as medians with interquartile ranges (IQR). To identify factors associated with mortality, the sample was divided into two groups : survivors and non-survivors (deceased). For the association between two qualitative variables, Pearson's chi-squared test was used (if conditions were met), otherwise Fisher's exact test. Multivariate analysis was conducted using a stepwise backward binary logistic regression model (selection threshold p = 0.2). The odds ratio (OR) with a 95% confidence interval was calculated to assess risk. The significance threshold was set at p ≤ 5%. 2.6. Conflict of interest : We declare that we have no conflicts of interest. 3. Results During the study, we included a total of 253 cases. This corresponds to an average prevalence of 1.2% compared to the total number of live births (Table 1). Table 1 : Prevalence of VLBW infants by years of study. Years of study Number of VLBW Number of live births Prevalence by live births (%) 2019 81 6095 1.3 2020 49 5165 0.95 2021 68 4471 1.5 2022 55 4471 1.2 2019-2022 253 20202 1.2 3.1. Maternal characteristics : Regarding maternal characteristics, the median age of mothers was 31 years, with the majority (70.8%) being between 20 and 35 years old. The majority of pregnancies were single (67.6%), 21.7% were twin, and 10.7% were multiple. The pregnancies were complicated by pre-eclampsia, premature rupture of membranes, and gestational diabetes in 29.2%, 19% and 16.6% of cases, respectively. Antenatal corticosteroid therapy was administered to the majority of women (72.4%). Caesarean section was necessary in 76.7% of cases (Table 2). 3.2. Neonatal characteristics : As for neonatal characteristics, the sex ratio was 0.96. The median gestational age at birth was 30 gestational weeks with extremes ranging from 25 to 37 weeks. Concerning birth weight, the median was 1280 grams with extremes ranging from 685 to 1490 g. Extreme prematurity (<28 gestational weeks) was observed in 13% of cases, while most patients (68%) were very preterm infants. Extremely low birth weight (< 1000g) was found in 12% of cases. Intrauterine growth restriction (IUGR) was diagnosed in 35.2% of newborns. Intubation in the delivery room was necessary for 17% of patients (Table 2). Table 2 : Maternal and neonatal characteristics. Characteristic Detail Percentage (%) Median [min-max] Maternal Median age of mothers - 31 years [18-44] Mothers aged from 20 to 35 years 70.8 - Single pregnancy 67.6 - Pre-eclampsia 29.2 - Premature rupture of membranes 19 - Gestational diabetes 16.6 - Antenatal corticosteroid therapy 72.4 - Cesarean section 76.7 - Neonatal Median gestational age at birth - 30 weeks [25-37] Median birth weight - 1280g [685-1490] Extreme prematurity (<28 Weeks) 13 - Extremely low birth weight (<1000g) 12 - Intrauterine growth restriction (IUGR) 35.2 - 5-min Apgar ≤ 7 25.3 - Intubation in the delivery room 17 - 3.3. Moribities : The study identified several significant morbidities among VLBW newborns. RDS was the most frequent morbidity, observed in 64% of cases. Nasal Continuous Positive Airway Pressure was the most commonly used initial ventilatory support, applied in 41.5% of cases. Surfactant was administered to 29.2% of cases. Mechanical ventilation was necessary for only 38.5% of patients. Ventilatory complications occurred in 35.5% of cases, with apnea being the most common (20.9%), followed by ventilator-associated pneumonia at 20.6%, and BPD in 5.9% of cases. Caffeine was prescribed to 79.4% of newborns. Regarding neurological complications, IVH was detected in 20.2%, with Grade III/IV observed in 6.7% of patients. Periventricular leukomalacia was noted in 3.2% of patients. A hemodynamically significant PDA was present in 28.5% of cases and was predominantly treated with paracetamol (83.3%). NEC occurred in 26.8% of patients. Lastly, nosocomial infections were diagnosed in 36% of VLBW neonates. The most frequent localization for these infections was pulmonary (ventilator-associated pneumonia) in 65.9% of cases. The most frequently isolated germ was Klebsiella Pneumoniae extended-spectrum β-lactamase (Table 3). Table 3 : Characteristics of morbidities among Very Low Birth Weight infants Morbidity Number Percentage (%) Key Characteristics/Treatment Hypothermia at admission (<36°C) 124 49 Incubators Respiratory distress syndrome 128 64 Surfactant (29.2%) Nasal Continuous Positive Airway Pressure (41.5%) Mechanical ventilation (38.5%) Median duration of oxygen therapy: 4 days. Caffeine (79.4%). Bronchopulmonary dysplasia 15 5.9 Inhaled corticosteroids (3.6%) Systemic corticosteroids (1.2%) Intraventricular Hemorrhage 51 20.2 Grade I: 7.5% Grade II: 6.7% Grade III: 2.4% Grade IV: 4.3% Periventricular leukomalacia 8 3.2 No treatment Seizure 12 4.7 Benzodiazepine Patent Ductus Arteriosus 60 28.5 paracetamol (83.3%). Ibuprofen (16.7%). Necrotizing Enterocolitis 68 26.8 Antibiotics Nosocomial Infections 91 36 Most frequent localization: Pulmonary (65.9%). Most frequently isolated germ: Klebsiella Pneumoniae extended-spectrum β-lactamase Catheterization, related to parenteral nutrition support, was necessary for all patients. Umbilical venous catheter was used as the first choice in 83.8% of cases, with a median duration of 6 days (IQR=5-9 days), and extremes from 1 to 17 days. Catheter-related complications were observed in 7.8% of cases. The specific types of complications reported were withdrawal (3.2%), infiltration (2.3%), hepatic abscess (1.8%), and occlusion (0.5%). Enteral feeding was successfully initiated in 91.3% of cases. The median age at the beginning of enteral feeding was 3 days (IQR = 1-6 days), with extremes ranging from 1 to 19 days. Exclusive maternal milk was used to initiate enteral feeding in 34.6% of cases. Artificial milk was used in 45.9% and mixed milk in 19.5%. Exclusive enteral feeding was achieved in 87.4% of cases. The median age for achieving exclusive enteral feeding was 10 days (IQR = 6-15 days), with extremes from 1 to 45 days. The median duration of hospitalization for the newborns was 29 days (IQR= 20-39 days), with extremes ranging from 1 to 226 days. The longest hospitalization of 226 days was observed in a newborn diagnosed with tricho-hepato-enteric syndrome, confirmed by genetic tests, due to chronic diarrhea. 3.4. Mortality : The study recorded 35 deaths, resulting in a mortality rate of 13.8%. This corresponds to a survival rate of 86.2%. The median age at death was 6 days (IQR = 3-18 days), with extremes ranging from 1 to 48 days. Nosocomial infection was identified as the most frequent cause of mortality (38.2%), followed by RDS (20.6%) and perinatal asphyxia (17.7%). No deaths were reported in newborns with a gestational age greater than 32 weeks. However, more than half (54%) of very low birth weight newborns born before 28 weeks of gestational age died. Among the nine newborns with a gestational age of 26 weeks, only one survived, leading to an 88% death rate for this group (Figure 1). The survival rate increased proportionally with birth weight; 53% of newborns weighing less than 1000g died, while the death rate was only 0.5% for newborns weighing over 1250g. 3.5. Predictive factors of mortality : The study identified several factors linked to mortality in VLBW newborns through both univariate and multivariate analyses. The multivariate analysis shows that mechanical ventilation was an independent factor associated with increased mortality, while non-invasive ventilation (NIV) was identified as a protective factor (OR < 1). Additionally, birth weight under 1000g, seizures, and catheter-related complications were associated with mortality. For gestational age, the study states that no deaths were reported for newborns with a gestational age greater than 32 weeks (Table 4). 4. Discussion VLBW infants represent a small but significant proportion of live births and a substantial portion of Neonatal Intensive Care Unit (NICU) admissions. They constitute 0.8% of live births in Taiwan. Despite this low prevalence, they are responsible for over 50% of perinatal deaths in this city (1). In Saudi Arabia, VLBW infants represent 1.43% of total live births. They also accounted for 15.4% of admissions to the NICU (6). In our institution, the prevalence of VLBW infants is comparable (1.2% of live births). Respiratory Distress Syndrome (RDS) is the most prevalent and significant acute pulmonary problem affecting VLBW infants (64% in our study). For example, in a study in Taiwan between 1997 and 2011, the incidence of RDS increased over time. It was the most common morbidity, rising from 78.7% in 1997-2001 to 88.5% in 2007-2011 (1). In a Turkish study of VLBW, nearly 70% of infants developed RDS (7). The management of RDS in VLBW infants has evolved significantly, primarily through surfactant therapy and advanced ventilatory strategies. It's noted that nasal Continuous Positive Airway Pressure (CPAP) has become a cornerstone of respiratory support (2). Applying CPAP soon after birth instead of early endotracheal intubation and mechanical ventilation is associated with a lower incidence of BPD. Routine use of CPAP immediately after delivery may decrease the need for intubation in infants and consequently its complications (8,9). Fortunately, in our study, 61.5% of infants avoided mechanical ventilation. So that we could explain the lower rate of BPD in our cohort (5.9%). In a study in Korea, the incidence of BPD increased from 17.8% to 33.0%, concurrent with a 31.4% decrease in overall mortality. This is attributed to the increased survival rate of VLBW infants, especially the most premature ones (10). Concerning the third morbidity found in our study, PDA was releaved in 28.5% of cases. PDA is a major neonatal morbidity for VLBW infants, contributing to a higher risk of mortality and prolonged hospitalization. Effectively, in the univariate analysis, PDA was associated to mortality (p<0.001). In a Turkish study of VLBW survivors, hemodynamically significant PDA was diagnosed in 24.8% of infants. For newborns with a gestational age of 32 weeks or less, this rate was 20.2% (7). Treatment approaches for PDA vary significantly between centers and have evolved. In one Belgian unit, PDA management shifted from prophylactic treatment in an earlier period (2000–2007) to treatment (2008–2012), and then to an expectative approach in the most recent period (2013–2020) (11). In a comparison between Canada and Japan, Canadian centers had lower rates of indomethacin administration but higher rates of PDA ligation compared to Japanese centers. Japanese neonatologists routinely used functional echocardiography to optimize circulatory management and provide earlier PDA treatment, which may have contributed to a reduction in severe IVH (12). In addition, the antenatal care could prevent IVH, such as antenatal corticosteroids and magnesium sulfate (11,13). Fortunately, many promoting procedures helped to ameliorate both mortality and morbidity, such as inhaled nitric oxide, caffeine, erythropoietin, neuroprotective surveillance, donor milk, probiotics, and lactoferrin (14–17). The rate of mortality varies from country to country and institution, which could be explained by the heterogeneity of the population and the differences in protocols of management. For example, in Japan and Canada, mortality was about 6.5% and 10.5% respectively (12). In a Chinese tertiary NICU, the overall mortality rate for VLBW infants dropped significantly from 26.1% in 2007-2011 to 13.1% in 2012-2016. This was associated with improvements in RDS outcomes and reduced need and duration of mechanical ventilation (2). Our results are similar to developed countries, registering 13.8% of mortality rate. The sex was not associated to mortality in our study, contrasting with other studies who reported survival and survival without morbidity consistently favorable to females throughout gestational age (18,19). As illustrated by our study and other articles, lower gestational age and birth weight are the most contributing factors of mortality (6). Also, lower Apgar score at minute 5, hypothermia, seizure, PDA, enterocolitis, and complicated catheterization are proven to be associated with a higher risk of mortality (20–22). It is important to consider that the main direct cause of mortality is nosocomial infections and sepsis. For that, prevention is important, by reducing the prescription of antibiotics, favorising human milk and probiotics, and respecting hygienic protocols (5,23,24). This study employed a descriptive analytical approach, which allows for an in-depth identification of risk factors associated with mortality in newborns. This methodology provides a solid foundation for formulating relevant hypotheses regarding factors influencing neonatal survival. But it was conducted in a single center: Neonatal Intensive Care of Monastir. This limits the generalizability of the results. Certain crucial aspects concerning management and morbidity evaluation were not included in the study. For instance, retinopathy, a significant concern due to its potential severe sequelae, was not explored in the newborns during their hospitalizations. This was attributed to a lack of necessary equipment and qualified personnel. 5. Conclusion Despite significant progress in neonatal intensive care, mortality among Very Low Birth Weight infants remains a major concern, particularly in developing countries such as Tunisia. In our study, mortality affected nearly one in seven VLBW infants, highlighting the fragility of this population. The leading causes of death were nosocomial infections, respiratory distress syndrome, and perinatal asphyxia, conditions that are largely preventable or manageable with optimal care. Several independent predictors of mortality were identified, notably extremely low birth weight (<1000g), seizure, catheter-related complications, and the need for mechanical ventilation. Conversely, the use of non-invasive ventilation emerged as a protective factor, underlining the importance of less invasive respiratory support strategies. These findings emphasize the need for targeted interventions to improve outcomes in VLBW infants. Strengthening infection prevention measures, optimizing catheter management, and promoting the early use of non-invasive ventilation could substantially reduce mortality. Furthermore, continuous training of healthcare professionals, adequate resource allocation, and national decisions prioritizing neonatal care are essential to achieving better survival rates. Ultimately, improving the prognosis of VLBW infants requires not only advanced medical care but also systemic strategies to ensure equitable and high-quality neonatal services across all regions. Abbreviations BPD : Broncho-Pulmonary Dysplasia CPAP : Continuous Positive Airway Pressure IQR : Interquartile Ranges IVH : Intra-Ventricular Hemorrhage IUGR : Intrauterine Growth Restriction NEC : Necrotising Enterocolitis NICU : Neonatal Intensive Care Unit NIV : Non-Invasive Ventilation OR : Odds Ratio PDA : Persistent Ductus Arteriosus RDS : Respiratory Distress Syndrome VLBW: Very Low Birth Weight Declarations Ethics approval and consent to participate: This study was conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. Approval was obtained from the Ethics Committee of the Teaching Hospital of Monastir. Due to the retrospective nature of the study, informed consent was waived. Consent for publication: Not applicable. Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors' contributions: MEO and SA conceptualized the study. RN and MB collected the data. FG, MG, and HBH analyzed the data. WD contributed to the statistical analysis. IG and RF contributed to obstetric data collection. KM supervised the study. All authors contributed to drafting and critically revising the manuscript. All authors read and approved the final version of the manuscript. Acknowledgement : The authors thank the medical and nursing staff of the Neonatal Intensive Care Unit of the Teaching Hospital of Monastir for their valuable assistance in patient care and data collection. References Su YY, Wang SH, Chou HC, Chen CY, Hsieh WS, Tsao PN, et al. Morbidity and mortality of very low birth weight infants in Taiwan-Changes in 15 years: A population based study. J Formos Med Assoc Taiwan Yi Zhi. déc 2016;115(12):1039‑45. Zhang T, Chen J, Wu H, Pan W, Yang X, Li Y, et al. Improved survival and survival without bronchopulmonary dysplasia in very low birth weight infants after active perinatal care. Niger J Clin Pract. juill 2020;23(7):980‑7. Lee J, Lee CYM, Naiduvaje K, Wong Y, Bhatia A, Ereno IL, et al. Trends in neonatal mortality and morbidity in very-low-birth-weight (VLBW) infants over a decade: Singapore national cohort study. Pediatr Neonatol. sept 2023;64(5):585‑95. Tapia JL, Toso A, Vaz Ferreira C, Fabres J, Musante G, Mariani G, et al. The unfinished work of neonatal very low birthweight infants quality improvement: Improving outcomes at a continental level in South America. Semin Fetal Neonatal Med. févr 2021;26(1):101193. Boo NY, Cheah IGS. Factors associated with inter-institutional variations in sepsis rates of very-low-birth-weight infants in 34 Malaysian neonatal intensive care units. Singapore Med J. mars 2016;57(3):144‑52. AlQurashi MA. Survival rate of very low birth weight infants over a quarter century (1994-2019): A single-institution experience. J Neonatal-Perinat Med. 2021;14(2):253‑60. Koc E, Demirel N, Bas AY, Isik DU, Hirfanoglu IM, Tunc T, et al. Early neonatal outcomes of very-low-birth-weight infants in Turkey: A prospective multicenter study of the Turkish Neonatal Society. PLOS ONE. 18 déc 2019;14(12):e0226679. Eichenwald EC, Stark AR. Management and Outcomes of Very Low Birth Weight. N Engl J Med. 2008;358(16):1700‑11. García-Muñoz Rodrigo F, Urquía Martí L, Galán Henríquez G, Rivero Rodríguez S, Tejera Carreño P, Molo Amorós S, et al. Perinatal risk factors for pneumothorax and morbidity and mortality in very low birth weight infants. J Matern-Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet. nov 2017;30(22):2679‑85. Jo HS, Cho KH, Cho SI, Song ES, Kim BI. Recent Changes in the Incidence of Bronchopulmonary Dysplasia among Very-Low-Birth-Weight Infants in Korea. J Korean Med Sci. oct 2015;30 Suppl 1(Suppl 1):S81-87. Vanhaesebrouck S, Zecic A, Goossens L, Keymeulen A, Garabedian L, De Meulemeester J, et al. Trends in neonatal morbidity and mortality for very low birthweight infants: a 20-year single-center experience. J Matern-Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet. déc 2023;36(2):2227311. Isayama T, Lee SK, Mori R, Kusuda S, Fujimura M, Ye XY, et al. Comparison of Mortality and Morbidity of Very Low Birth Weight Infants Between Canada and Japan. PEDIATRICS. 2012;130(4):e957‑65. Vaz Ferreira C, Caro J, Villarroel L, Muñoz S, Alvarez P, Flores G, et al. Antenatal exposure to magnesium sulfate and neonatal outcomes in very low birth weight infants: a multicenter study. J Perinatol Off J Calif Perinat Assoc. nov 2024;44(11):1663‑8. Costescu OC, Boia ER, Boia M, Cioboata DM, Doandes FM, Lungu N, et al. The Role of Erythropoietin in Preventing Anemia in the Premature Neonate. Children. déc 2023;10(12):1843. Corpeleijn WE, Waard M de, Christmann V, Goudoever JB van, Weide MCJ der, Kooi EMW, et al. Effect of Donor Milk on Severe Infections and Mortality in Very Low-Birth-Weight Infants. JAMA Pediatr. 2016;170(7):654‑654. Tarnow-Mordi WO, Abdel-Latif ME, Martin A, Pammi M, Robledo K, Manzoni P, et al. The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial. Lancet Child Adolesc Health. juin 2020;4(6):444‑54. Kanic Z, Micetic Turk D, Burja S, Kanic V, Dinevski D. Influence of a combination of probiotics on bacterial infections in very low birthweight newborns. Wien Klin Wochenschr. déc 2015;127 Suppl 5:S210-215. García-Muñoz Rodrigo F, Fabres JG, Zozaya Nieto C, San Feliciano L, Figueras-Aloy J, Saenz de Pipaon M, et al. Survival and Survival without Major Morbidity Seem to Be Consistently Better throughout Gestational Age in 24- to 30-Week Gestational Age Very-Low-Birth-Weight Female Infants Compared to Males. Neonatology. 2022;119(5):585‑93. Vu HD, Dickinson C, Kandasamy Y. Sex Difference in Mortality for Premature and Low Birth Weight Neonates: A Systematic Review. Am J Perinatol. 14 déc 2017;35:707‑15. de Almeida MFB, Moreira LMO, Vaz dos Santos RM, Kawakami MD, Anchieta LM, Guinsburg R. Early neonatal deaths with perinatal asphyxia in very low birth weight Brazilian infants. J Perinatol Off J Calif Perinat Assoc. nov 2015;35(11):954‑7. Youn YA, Kim EK, Kim SY. Necrotizing Enterocolitis among Very-Low-Birth-Weight Infants in Korea. J Korean Med Sci. oct 2015;30 Suppl 1(Suppl 1):S75-80. Jammeh ML, Adibe OO, Tracy ET, Rice HE, Clark RH, Smith PB, et al. Racial/ethnic differences in necrotizing enterocolitis incidence and outcomes in premature very low birth weight infants. J Perinatol Off J Calif Perinat Assoc. oct 2018;38(10):1386‑90. Ting JY, Synnes A, Roberts A, Deshpandey A, Dow K, Yoon EW, et al. Association Between Antibiotic Use and Neonatal Mortality and Morbidities in Very Low-Birth-Weight Infants Without Culture-Proven Sepsis or Necrotizing Enterocolitis. JAMA Pediatr. 1 déc 2016;170(12):1181‑7. Cantey JB, Anderson KR, Kalagiri RR, Mallett LH. Morbidity and mortality of coagulase-negative staphylococcal sepsis in very-low-birth-weight infants. World J Pediatr WJP. juin 2018;14(3):269‑73. Additional Declarations No competing interests reported. Supplementary Files Additionalfile1.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 25 Mar, 2026 Reviews received at journal 01 Nov, 2025 Reviews received at journal 01 Nov, 2025 Reviews received at journal 26 Oct, 2025 Reviewers agreed at journal 23 Oct, 2025 Reviewers agreed at journal 23 Oct, 2025 Reviewers agreed at journal 22 Oct, 2025 Reviewers agreed at journal 21 Oct, 2025 Reviewers invited by journal 21 Oct, 2025 Editor invited by journal 07 Oct, 2025 Editor assigned by journal 06 Oct, 2025 Submission checks completed at journal 06 Oct, 2025 First submitted to journal 30 Sep, 2025 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7754946","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":535172808,"identity":"a69868e3-fc20-4fec-a0cf-b4ef14f119ca","order_by":0,"name":"Maroua El Ouaer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA90lEQVRIiWNgGAWjYDADPghlA8SMjQeI0sIGodJAWhpI0nIYTOLVott+9uFjnhoGOTb2HsMPH/ect1vbfhhoS41NNC4tZmfSjY15jjEYs/GcMZac8ex28rYziUAtx9JyG3BpOZDGJs3DxpDYJpFjIM1z4Hay2QGgFsaGw7i1nH8G1PKPoR6oxfj3nwPnks3OPySg5QbQFt42hgQ2iRwzaYYDB+zMbhCy5cYzZsO5fRKGbTzHyix7DiQnmN0A2pKAzy/n0xgfvPlmI8/P3rz5xo8DdvZm59MfPvhQY4NTCxRIwFmJYJUJ+JWjAntSFI+CUTAKRsHIAADbYl0hAzTokAAAAABJRU5ErkJggg==","orcid":"","institution":"University of Monastir","correspondingAuthor":true,"prefix":"","firstName":"Maroua","middleName":"El","lastName":"Ouaer","suffix":""},{"id":535172809,"identity":"c23791b8-6879-478b-a325-6f52e922b99c","order_by":1,"name":"Siwar Abdelmoula","email":"","orcid":"","institution":"University of Monastir","correspondingAuthor":false,"prefix":"","firstName":"Siwar","middleName":"","lastName":"Abdelmoula","suffix":""},{"id":535172810,"identity":"26fdc846-f46a-4c16-8b37-0f7bfe1aac7b","order_by":2,"name":"Rania Naffeti","email":"","orcid":"","institution":"University of Monastir","correspondingAuthor":false,"prefix":"","firstName":"Rania","middleName":"","lastName":"Naffeti","suffix":""},{"id":535172811,"identity":"ddd1871e-d755-41b4-a483-1899babba99f","order_by":3,"name":"Hayet Ben Hamida","email":"","orcid":"","institution":"University of Monastir","correspondingAuthor":false,"prefix":"","firstName":"Hayet","middleName":"Ben","lastName":"Hamida","suffix":""},{"id":535172812,"identity":"48843b57-695a-4a6e-9951-8cb356a814ce","order_by":4,"name":"Fedia Guedouar","email":"","orcid":"","institution":"University of Monastir","correspondingAuthor":false,"prefix":"","firstName":"Fedia","middleName":"","lastName":"Guedouar","suffix":""},{"id":535172813,"identity":"ad328d5a-0800-4f18-95a6-9e3da614d3fe","order_by":5,"name":"Maha Ghali","email":"","orcid":"","institution":"University of Monastir","correspondingAuthor":false,"prefix":"","firstName":"Maha","middleName":"","lastName":"Ghali","suffix":""},{"id":535172814,"identity":"1afde0dd-5dfa-4d9c-9f34-cd71c351ade8","order_by":6,"name":"Manel Bizid","email":"","orcid":"","institution":"University of Monastir","correspondingAuthor":false,"prefix":"","firstName":"Manel","middleName":"","lastName":"Bizid","suffix":""},{"id":535172815,"identity":"085bdae2-c56c-4bec-b251-e593932c76f4","order_by":7,"name":"Wafa Dhouib","email":"","orcid":"","institution":"University of Monastir","correspondingAuthor":false,"prefix":"","firstName":"Wafa","middleName":"","lastName":"Dhouib","suffix":""},{"id":535172816,"identity":"28eb2461-b579-4823-9a93-c95c9d6f2aae","order_by":8,"name":"Imen Ghadhab","email":"","orcid":"","institution":"University of Monastir","correspondingAuthor":false,"prefix":"","firstName":"Imen","middleName":"","lastName":"Ghadhab","suffix":""},{"id":535172818,"identity":"0cc22173-50b7-4bce-bb7a-8a1c204acf32","order_by":9,"name":"Raja Faleh","email":"","orcid":"","institution":"University of Monastir","correspondingAuthor":false,"prefix":"","firstName":"Raja","middleName":"","lastName":"Faleh","suffix":""},{"id":535172819,"identity":"31af0856-b322-4a7c-b6bd-99cbb01b41fd","order_by":10,"name":"Kamel Monastiri","email":"","orcid":"","institution":"University of Monastir","correspondingAuthor":false,"prefix":"","firstName":"Kamel","middleName":"","lastName":"Monastiri","suffix":""}],"badges":[],"createdAt":"2025-09-30 21:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7754946/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7754946/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":94846082,"identity":"12b7a1d0-6997-4dad-9adc-98489c5c15b6","added_by":"auto","created_at":"2025-10-31 10:11:00","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":96998,"visible":true,"origin":"","legend":"","description":"","filename":"VLBWarticle.docx","url":"https://assets-eu.researchsquare.com/files/rs-7754946/v1/240e96304a9510781fce1efe.docx"},{"id":94846085,"identity":"4cdc398a-d81f-4f7f-9428-e6f84ebfeec0","added_by":"auto","created_at":"2025-10-31 10:11:01","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":11368,"visible":true,"origin":"","legend":"","description":"","filename":"54eb4cb03a4a483e9ccd13fd32a21ca6.json","url":"https://assets-eu.researchsquare.com/files/rs-7754946/v1/59c375abc017eafbb50cfd0d.json"},{"id":94846083,"identity":"4cf6f7e8-4189-43c3-9e78-882d25e50205","added_by":"auto","created_at":"2025-10-31 10:11:00","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":74784,"visible":true,"origin":"","legend":"","description":"","filename":"54eb4cb03a4a483e9ccd13fd32a21ca61enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7754946/v1/fc107a902f0d96e57842a35b.xml"},{"id":94846084,"identity":"2c69a86e-0c12-4963-be91-ba3f1406adca","added_by":"auto","created_at":"2025-10-31 10:11:00","extension":"xml","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":73018,"visible":true,"origin":"","legend":"","description":"","filename":"54eb4cb03a4a483e9ccd13fd32a21ca61structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7754946/v1/bed9a884dcace414585f2b39.xml"},{"id":94846086,"identity":"11ce3a6a-d0e3-4187-aaef-9cf7d69688b2","added_by":"auto","created_at":"2025-10-31 10:11:01","extension":"html","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":84059,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7754946/v1/ba0ba27e10f72f4779fd3688.html"},{"id":94846079,"identity":"038b0923-8716-4ea0-b72f-3be49f06bee5","added_by":"auto","created_at":"2025-10-31 10:11:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":46820,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eVariation of rates of mortality and survival by gestational weeks and birth weight.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7754946/v1/950b988250d032a3a7a7ac45.png"},{"id":94985022,"identity":"e94885e3-ab41-49fb-93da-99cab0ff781f","added_by":"auto","created_at":"2025-11-03 06:57:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":910788,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7754946/v1/ced0c484-4571-40be-9094-ec8d0ac9887d.pdf"},{"id":94846078,"identity":"408f0503-d643-4068-afd6-1c6011414b9b","added_by":"auto","created_at":"2025-10-31 10:11:00","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":23153,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7754946/v1/dca1b6cc273869c3c1599089.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Short-term outcomes and predictive factors of mortality among Very Low Birth Weight newborns (\u003c 1500g): cross-sectional study in the Neonatal Intensive Care Unit of Monastir, Tunisia.","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eVLBW infants are defined as newborns with a body weight of less than 1500 grams at birth (1). Premature birth, including VLBW, is the leading cause of infant mortality worldwide, with an estimated 28% of global neonatal deaths directly attributable to it (2). Despite the improvement of the management in neonatal intensive care units, VLBW infants still have a high rate of mortalities and record morbidities, especially in developing countries (1,3). Common complications include Respiratory Distress Syndrome, Patent Ductus Arteriosus, sepsis, necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, and retinopathy of prematurity. These conditions prolong hospitalization and increase healthcare costs (4). Additionally, late-onset sepsis remains a major concern in VLBW infant care (5).\u003c/p\u003e\u003cp\u003eTherefore, understanding the predictive factors of mortality, evolving clinical practices, and neonatal outcomes in VLBW infants is crucial for improving their future health. Studying these trends and identifying disparities in outcomes and care practices allows the development of targeted strategies to minimize adverse outcomes and optimize care for these vulnerable newborns.\u003c/p\u003e\u003cp\u003eThe aims of this study are to describe the rate of mortality and morbidity among VLBW neonates and also to identify predictive factors of mortality.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Study design and setting :\u003c/h2\u003e\u003cp\u003e We conducted a cross-sectional study in the Neonatal Intensive Care Unit of the Teaching Hospital Fattouma Bourguiba in Monastir, which serves the central and southern regions of Tunisia. This unit is a third level unit, and one of the six units of Tunisia. The period of the study is four years, from january 2019 to december 2022.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Participants :\u003c/h2\u003e\u003cp\u003eWe included all newborns with VLBW (less than 1500g) regardless of gestational age. We excluded VLBW infants with chromosomal abnormalities, congenital heart defects, and other malformations incompatible with life. Infants who died in the delivery room were not included.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Study size :\u003c/h2\u003e\u003cp\u003eThis was an exhaustive study including all VLBW newborns meeting the inclusion and exclusion criteria throughout the study period.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Variables :\u003c/h2\u003e\u003cp\u003eData was collected retrospectively from medical records using a pre-established collection form. Variables extracted included antenatal care, corticosteroid use, gestational age, birth weight, ventilation use, and enteral nutrition.\u003c/p\u003e\u003cp\u003eMortality was defined as death before discharge from the hospital. The following morbidities were releaved : Respiratory Distress Syndrome (RDS) based on clinical findings and chest X-ray radiography, Intra-Ventricular Hemorrhage (IVH) diagnosed by brain ultrasonography, Persistent Ductus Arteriosus (PDA) confirmed by echocardiography realized by a neonatologist or cardiopediatrician, Necrotising Enterocolitis (NEC) diagnosed by radiography and clinical symptoms, Nosocomial infection confirmed by blood culture and based on clinical symptoms and Broncho-Pulmonary Dysplasia (BPD) defined as the need for supplemental oxygen at 36 weeks' postmenstrual age.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5. Statistical methods:\u003c/h2\u003e\u003cp\u003eStatistical analysis was performed using SPSS (Statistical Package for the Social Sciences) version 21. Qualitative variables were described by counts and percentages. Quantitative variables were assessed for distribution using the Kolmogorov-Smirnov test. Variables following a normal distribution were reported as means and standard deviations, while those not following a normal distribution were reported as medians with interquartile ranges (IQR).\u003c/p\u003e\u003cp\u003eTo identify factors associated with mortality, the sample was divided into two groups : survivors and non-survivors (deceased).\u003c/p\u003e\u003cp\u003eFor the association between two qualitative variables, Pearson's chi-squared test was used (if conditions were met), otherwise Fisher's exact test.\u003c/p\u003e\u003cp\u003eMultivariate analysis was conducted using a stepwise backward binary logistic regression model (selection threshold p\u0026thinsp;=\u0026thinsp;0.2). The odds ratio (OR) with a 95% confidence interval was calculated to assess risk. The significance threshold was set at p\u0026thinsp;\u0026le;\u0026thinsp;5%.\u003c/p\u003e\u003c/div\u003e\n\u003cp\u003e2.6. Conflict of interest\u0026nbsp;:\u003c/p\u003e\n\u003cp\u003eWe declare that we have no conflicts of interest.\u003c/p\u003e"},{"header":"3.\tResults ","content":"\u003cp\u003eDuring the study, we included a total of 253 cases. This corresponds to an average prevalence of 1.2% compared to the total number of live births (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;: Prevalence of VLBW infants by years of study.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cem\u003eYears of study\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cem\u003eNumber of VLBW\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u003cem\u003eNumber of live births\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003e\u003cem\u003ePrevalence by live births (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cem\u003e2019\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e6095\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cem\u003e2020\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e5165\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cem\u003e2021\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e4471\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cem\u003e2022\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e4471\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cem\u003e2019-2022\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e253\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e20202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 215px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3.1. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Maternal characteristics :\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRegarding maternal characteristics, the median age of mothers was 31 years, with the majority (70.8%) being between 20 and 35 years old. The majority of pregnancies were single (67.6%), 21.7% were twin, and 10.7% were multiple. The pregnancies were complicated by pre-eclampsia, premature rupture of membranes, and gestational diabetes in 29.2%, 19% and 16.6% of cases, respectively. Antenatal corticosteroid therapy was administered to the majority of women (72.4%). Caesarean section was necessary in 76.7% of cases (Table 2).\u003c/p\u003e\n\u003cp\u003e3.2. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Neonatal characteristics :\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs for neonatal characteristics, the sex ratio was 0.96. The median gestational age at birth was 30 gestational weeks with extremes ranging from 25 to 37 weeks. Concerning birth weight, the median was 1280 grams with extremes ranging from 685 to 1490 g. Extreme prematurity (\u0026lt;28 gestational weeks) was observed in 13% of cases, while most patients (68%) were very preterm infants. Extremely low birth weight (\u0026lt; 1000g) was found in 12% of cases. Intrauterine growth restriction (IUGR) was diagnosed in 35.2% of newborns. Intubation in the delivery room was necessary for 17% of patients (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u0026nbsp;: Maternal and neonatal characteristics.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"633\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eCharacteristic\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eDetail\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePercentage (%)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMedian [min-max]\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMaternal\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedian age of mothers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e31 years [18-44]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMothers aged from 20 to 35 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e70.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSingle pregnancy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e67.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePre-eclampsia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e29.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePremature rupture of membranes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGestational diabetes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAntenatal corticosteroid therapy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e72.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCesarean section\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e76.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eNeonatal\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedian gestational age at birth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e30 weeks [25-37]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMedian birth weight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1280g [685-1490]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eExtreme prematurity (\u0026lt;28 Weeks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eExtremely low birth weight (\u0026lt;1000g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIntrauterine growth restriction (IUGR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e35.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5-min Apgar \u003cstrong\u003e\u0026le; 7\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIntubation in the delivery room\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e3.3. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Moribities :\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study identified several significant morbidities among VLBW newborns. RDS\u0026nbsp;was the most frequent morbidity, observed in 64% of cases. Nasal Continuous Positive Airway Pressure\u0026nbsp;was the most commonly used initial ventilatory support, applied in 41.5% of cases. Surfactant was administered to 29.2% of cases. Mechanical ventilation was necessary for only 38.5% of patients. Ventilatory complications occurred in 35.5% of cases, with apnea being the most common (20.9%), followed by ventilator-associated pneumonia at 20.6%, and BPD in 5.9% of cases. Caffeine was prescribed to 79.4% of newborns.\u003c/p\u003e\n\u003cp\u003eRegarding neurological complications, IVH was detected in 20.2%,\u0026nbsp;with Grade III/IV observed in 6.7% of patients. Periventricular leukomalacia was noted in 3.2% of patients. A hemodynamically significant PDA was present in 28.5% of cases and was predominantly treated with paracetamol (83.3%).\u003c/p\u003e\n\u003cp\u003eNEC occurred in 26.8% of patients. Lastly, nosocomial infections were diagnosed in 36% of VLBW neonates. The most frequent localization for these infections was pulmonary (ventilator-associated pneumonia) in 65.9% of cases. The most frequently isolated germ was \u003cem\u003eKlebsiella Pneumoniae\u003c/em\u003e extended-spectrum \u0026beta;-lactamase (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;: Characteristics of morbidities among Very Low Birth Weight infants\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"680\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 145px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMorbidity\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eNumber\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePercentage (%)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 339px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eKey Characteristics/Treatment\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 145px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eHypothermia at admission (\u0026lt;36\u0026deg;C)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 339px;\"\u003e\n \u003cp\u003eIncubators\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 145px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eRespiratory distress syndrome\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 339px;\"\u003e\n \u003cp\u003eSurfactant (29.2%)\u003c/p\u003e\n \u003cp\u003eNasal Continuous Positive Airway Pressure (41.5%)\u003c/p\u003e\n \u003cp\u003eMechanical ventilation (38.5%)\u003c/p\u003e\n \u003cp\u003eMedian duration of oxygen therapy: 4 days.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eCaffeine \u0026nbsp;(79.4%).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 145px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eBronchopulmonary dysplasia\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 339px;\"\u003e\n \u003cp\u003eInhaled corticosteroids (3.6%)\u003c/p\u003e\n \u003cp\u003eSystemic corticosteroids (1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 145px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eIntraventricular Hemorrhage\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e20.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 339px;\"\u003e\n \u003cp\u003eGrade I: 7.5%\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eGrade II: 6.7%\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eGrade III: 2.4%\u003c/p\u003e\n \u003cp\u003eGrade IV: 4.3%\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 145px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePeriventricular leukomalacia\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e3.2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 339px;\"\u003e\n \u003cp\u003eNo treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 145px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSeizure\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 339px;\"\u003e\n \u003cp\u003eBenzodiazepine\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 145px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatent Ductus Arteriosus\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e28.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 339px;\"\u003e\n \u003cp\u003eparacetamol (83.3%).\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eIbuprofen (16.7%).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 145px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eNecrotizing Enterocolitis\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e26.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 339px;\"\u003e\n \u003cp\u003eAntibiotics\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 145px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eNosocomial Infections\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 127px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 339px;\"\u003e\n \u003cp\u003eMost frequent localization: Pulmonary (65.9%).\u003c/p\u003e\n \u003cp\u003eMost frequently isolated germ:\u003cem\u003e\u0026nbsp;Klebsiella Pneumoniae\u003c/em\u003e extended-spectrum \u0026beta;-lactamase\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCatheterization, related to parenteral nutrition support, was necessary for all patients. Umbilical venous catheter was used as the first choice in 83.8% of cases, with a median duration of 6 days (IQR=5-9 days), and extremes from 1 to 17 days. Catheter-related complications were observed in 7.8% of cases. The specific types of complications reported were withdrawal (3.2%), infiltration (2.3%), hepatic abscess (1.8%), and occlusion (0.5%).\u003c/p\u003e\n\u003cp\u003eEnteral feeding was successfully initiated in 91.3% of cases. The median age at the beginning of enteral feeding was 3 days (IQR = 1-6 days), with extremes ranging from 1 to 19 days. Exclusive maternal milk was used to initiate enteral feeding in 34.6% of cases. Artificial milk was used in 45.9% and mixed milk in 19.5%. Exclusive enteral feeding was achieved in 87.4% of cases. The median age for achieving exclusive enteral feeding was 10 days (IQR = 6-15 days), with extremes from 1 to 45 days.\u003c/p\u003e\n\u003cp\u003eThe median duration of hospitalization for the newborns was 29 days (IQR= 20-39 days), with extremes ranging from 1 to 226 days.\u003c/p\u003e\n\u003cp\u003eThe longest hospitalization of 226 days was observed in a newborn diagnosed with tricho-hepato-enteric syndrome, confirmed by genetic tests, due to chronic diarrhea.\u003c/p\u003e\n\u003cp\u003e3.4. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Mortality :\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study recorded 35 deaths, resulting in a mortality rate of 13.8%. This corresponds to a survival rate of 86.2%. The median age at death was 6 days (IQR = 3-18 days), with extremes ranging from 1 to 48 days.\u003c/p\u003e\n\u003cp\u003eNosocomial infection was identified as the most frequent cause of mortality (38.2%), followed by RDS (20.6%) and perinatal asphyxia (17.7%).\u003c/p\u003e\n\u003cp\u003eNo deaths were reported in newborns with a gestational age greater than 32 weeks. However, more than half (54%) of very low birth weight newborns born before 28 weeks of gestational age died. Among the nine newborns with a gestational age of 26 weeks, only one survived, leading to an 88% death rate for this group (Figure 1).\u003c/p\u003e\n\u003cp\u003eThe survival rate increased proportionally with birth weight; 53% of newborns weighing less than 1000g died, while the death rate was only 0.5% for newborns weighing over 1250g.\u003c/p\u003e\n\u003cp\u003e3.5.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Predictive factors of mortality :\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study identified several factors linked to mortality in VLBW newborns through both univariate and multivariate analyses. The multivariate analysis shows that mechanical ventilation was an independent factor associated with increased mortality, while non-invasive ventilation (NIV) was identified as a protective factor (OR \u0026lt; 1). Additionally, birth weight under 1000g, seizures, and catheter-related complications were associated with mortality. For gestational age, the study states that no deaths were reported for newborns with a gestational age greater than 32 weeks (Table 4).\u003c/p\u003e"},{"header":"4.\tDiscussion","content":"\u003cp\u003eVLBW infants represent a small but significant proportion of live births and a substantial portion of Neonatal Intensive Care Unit (NICU) admissions. They constitute 0.8% of live births in Taiwan. Despite this low prevalence, they are responsible for over 50% of perinatal deaths in this city (1). In Saudi Arabia, VLBW infants\u0026nbsp;represent 1.43% of total live births.\u0026nbsp;They also accounted for 15.4% of admissions to the NICU (6). In our institution, the prevalence of VLBW infants is comparable (1.2% of live births).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRespiratory Distress Syndrome (RDS) is the most prevalent and significant acute pulmonary problem affecting VLBW infants (64% in our study).\u003c/p\u003e\n\u003cp\u003eFor example, in a study in Taiwan between 1997 and 2011, the incidence of RDS increased over time. It was the most common morbidity, rising from 78.7% in 1997-2001 to 88.5% in 2007-2011 (1). In a Turkish study of VLBW, nearly 70% of infants developed RDS (7).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe management of RDS in VLBW infants has evolved significantly, primarily through surfactant therapy and advanced ventilatory strategies.\u003c/p\u003e\n\u003cp\u003eIt\u0026apos;s noted that nasal Continuous Positive Airway Pressure (CPAP) has become a cornerstone of respiratory support (2). Applying CPAP soon after birth instead of early endotracheal intubation and mechanical ventilation is associated with a lower incidence of BPD. Routine use of CPAP immediately after delivery may decrease the need for intubation in infants and consequently its complications (8,9). Fortunately, in our study, 61.5% of infants avoided mechanical ventilation. So that we could explain the lower rate of BPD in our cohort (5.9%).\u003c/p\u003e\n\u003cp\u003eIn a study in Korea, the incidence of BPD increased from 17.8% to 33.0%, concurrent with a 31.4% decrease in overall mortality. This is attributed to the increased survival rate of VLBW infants, especially the most premature ones (10).\u003c/p\u003e\n\u003cp\u003eConcerning the third morbidity found in our study, PDA was releaved in 28.5% of cases.\u0026nbsp;PDA is a major neonatal morbidity for VLBW infants, contributing to a higher risk of mortality and prolonged hospitalization. Effectively,\u0026nbsp;in the univariate analysis, PDA was associated to mortality (p\u0026lt;0.001). In a Turkish study of VLBW survivors, hemodynamically significant PDA was diagnosed in 24.8% of infants. For newborns with a gestational age of 32 weeks or less, this rate was 20.2% (7). Treatment approaches for PDA vary significantly between centers and have evolved. In one Belgian unit, PDA management shifted from prophylactic treatment in an earlier period (2000\u0026ndash;2007) to treatment (2008\u0026ndash;2012), and then to an expectative approach in the most recent period (2013\u0026ndash;2020) (11). In a comparison between Canada and Japan, Canadian centers had lower rates of indomethacin administration but higher rates of PDA ligation compared to Japanese centers. Japanese neonatologists routinely used functional echocardiography to optimize circulatory management and provide earlier PDA treatment, which may have contributed to a reduction in severe IVH (12). In addition, the antenatal care could prevent IVH, such as antenatal corticosteroids and magnesium sulfate (11,13).\u0026nbsp;Fortunately, many promoting procedures helped to ameliorate both mortality and morbidity, such as inhaled nitric oxide, caffeine, erythropoietin, neuroprotective surveillance, donor milk, probiotics, and lactoferrin (14\u0026ndash;17).\u003c/p\u003e\n\u003cp\u003eThe rate of mortality varies from country to country and institution, which could be explained by the heterogeneity of the population and the differences in protocols of management. For example, in Japan and Canada, mortality was about 6.5% and 10.5% respectively (12).\u003c/p\u003e\n\u003cp\u003eIn a Chinese tertiary NICU, the overall mortality rate for VLBW infants dropped significantly from 26.1% in 2007-2011 to 13.1% in 2012-2016. This was associated with improvements in RDS outcomes and reduced need and duration of mechanical ventilation (2). Our results are similar to developed countries, registering 13.8% of mortality rate.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe sex was not associated to mortality in our study, contrasting with other studies who reported survival and survival without morbidity consistently favorable to females throughout gestational age (18,19).\u003c/p\u003e\n\u003cp\u003eAs illustrated by our study and other articles, lower gestational age and birth weight are the most contributing factors of mortality (6). Also, lower Apgar score at minute 5, hypothermia, seizure, PDA, enterocolitis, and complicated catheterization are proven to be associated with a higher risk of mortality (20\u0026ndash;22). It is important to consider that the main direct cause of mortality is nosocomial infections and sepsis. For that, prevention is important, by reducing the prescription of antibiotics, favorising human milk and probiotics, and respecting hygienic protocols (5,23,24).\u003c/p\u003e\n\u003cp\u003eThis study employed a descriptive analytical approach, which allows for an in-depth identification of risk factors associated with mortality in newborns. This methodology provides a solid foundation for formulating relevant hypotheses regarding factors influencing neonatal survival.\u003c/p\u003e\n\u003cp\u003eBut it was conducted in a single center: Neonatal Intensive Care of Monastir. This limits the generalizability of the results.\u003c/p\u003e\n\u003cp\u003eCertain crucial aspects concerning management and morbidity evaluation were not included in the study. For instance, retinopathy, a significant concern due to its potential severe sequelae, was not explored in the newborns during their hospitalizations. This was attributed to a lack of necessary equipment and qualified personnel.\u003c/p\u003e"},{"header":"5.\tConclusion ","content":"\u003cp\u003eDespite significant progress in neonatal intensive care, mortality among Very Low Birth Weight infants remains a major concern, particularly in developing countries such as Tunisia. In our study, mortality affected nearly one in seven VLBW infants, highlighting the fragility of this population. The leading causes of death were nosocomial infections, respiratory distress syndrome, and perinatal asphyxia, conditions that are largely preventable or manageable with optimal care.\u003c/p\u003e\n\u003cp\u003eSeveral independent predictors of mortality were identified, notably extremely low birth weight (\u0026lt;1000g), seizure, catheter-related complications, and the need for mechanical ventilation. Conversely, the use of non-invasive ventilation emerged as a protective factor, underlining the importance of less invasive respiratory support strategies.\u003c/p\u003e\n\u003cp\u003eThese findings emphasize the need for targeted interventions to improve outcomes in VLBW infants. Strengthening infection prevention measures, optimizing catheter management, and promoting the early use of non-invasive ventilation could substantially reduce mortality. Furthermore, continuous training of healthcare professionals, adequate resource allocation, and national decisions prioritizing neonatal care are essential to achieving better survival rates.\u003c/p\u003e\n\u003cp\u003eUltimately, improving the prognosis of VLBW infants requires not only advanced medical care but also systemic strategies to ensure equitable and high-quality neonatal services across all regions.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBPD : Broncho-Pulmonary Dysplasia\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCPAP : Continuous Positive Airway Pressure\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIQR : Interquartile Ranges\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIVH : Intra-Ventricular Hemorrhage\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIUGR : Intrauterine Growth Restriction\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNEC : Necrotising Enterocolitis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNICU\u0026nbsp;: Neonatal Intensive Care Unit\u003c/p\u003e\n\u003cp\u003eNIV : Non-Invasive Ventilation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOR : Odds Ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePDA : Persistent Ductus Arteriosus\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRDS : Respiratory Distress Syndrome\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eVLBW: Very Low Birth Weight\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e This study was conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. Approval was obtained from the Ethics Committee of the Teaching Hospital of Monastir. Due to the retrospective nature of the study, informed consent was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e MEO and SA conceptualized the study. RN and MB collected the data. FG, MG, and HBH analyzed the data. WD contributed to the statistical analysis. IG and RF contributed to obstetric data collection. KM supervised the study. All authors contributed to drafting and critically revising the manuscript. All authors read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e: The authors thank the medical and nursing staff of the Neonatal Intensive Care Unit of the Teaching Hospital of Monastir for their valuable assistance in patient care and data collection.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSu YY, Wang SH, Chou HC, Chen CY, Hsieh WS, Tsao PN, et al. Morbidity and mortality of very low birth weight infants in Taiwan-Changes in 15 years: A population based study. J Formos Med Assoc Taiwan Yi Zhi. d\u0026eacute;c 2016;115(12):1039‑45. \u003c/li\u003e\n\u003cli\u003eZhang T, Chen J, Wu H, Pan W, Yang X, Li Y, et al. Improved survival and survival without bronchopulmonary dysplasia in very low birth weight infants after active perinatal care. Niger J Clin Pract. juill 2020;23(7):980‑7. \u003c/li\u003e\n\u003cli\u003eLee J, Lee CYM, Naiduvaje K, Wong Y, Bhatia A, Ereno IL, et al. Trends in neonatal mortality and morbidity in very-low-birth-weight (VLBW) infants over a decade: Singapore national cohort study. Pediatr Neonatol. sept 2023;64(5):585‑95. \u003c/li\u003e\n\u003cli\u003eTapia JL, Toso A, Vaz Ferreira C, Fabres J, Musante G, Mariani G, et al. The unfinished work of neonatal very low birthweight infants quality improvement: Improving outcomes at a continental level in South America. Semin Fetal Neonatal Med. f\u0026eacute;vr 2021;26(1):101193. \u003c/li\u003e\n\u003cli\u003eBoo NY, Cheah IGS. Factors associated with inter-institutional variations in sepsis rates of very-low-birth-weight infants in 34 Malaysian neonatal intensive care units. Singapore Med J. mars 2016;57(3):144‑52. \u003c/li\u003e\n\u003cli\u003eAlQurashi MA. Survival rate of very low birth weight infants over a quarter century (1994-2019): A single-institution experience. J Neonatal-Perinat Med. 2021;14(2):253‑60. \u003c/li\u003e\n\u003cli\u003eKoc E, Demirel N, Bas AY, Isik DU, Hirfanoglu IM, Tunc T, et al. Early neonatal outcomes of very-low-birth-weight infants in Turkey: A prospective multicenter study of the Turkish Neonatal Society. PLOS ONE. 18 d\u0026eacute;c 2019;14(12):e0226679. \u003c/li\u003e\n\u003cli\u003eEichenwald EC, Stark AR. Management and Outcomes of Very Low Birth Weight. N Engl J Med. 2008;358(16):1700‑11. \u003c/li\u003e\n\u003cli\u003eGarc\u0026iacute;a-Mu\u0026ntilde;oz Rodrigo F, Urqu\u0026iacute;a Mart\u0026iacute; L, Gal\u0026aacute;n Henr\u0026iacute;quez G, Rivero Rodr\u0026iacute;guez S, Tejera Carre\u0026ntilde;o P, Molo Amor\u0026oacute;s S, et al. Perinatal risk factors for pneumothorax and morbidity and mortality in very low birth weight infants. J Matern-Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet. nov 2017;30(22):2679‑85. \u003c/li\u003e\n\u003cli\u003eJo HS, Cho KH, Cho SI, Song ES, Kim BI. Recent Changes in the Incidence of Bronchopulmonary Dysplasia among Very-Low-Birth-Weight Infants in Korea. J Korean Med Sci. oct 2015;30 Suppl 1(Suppl 1):S81-87. \u003c/li\u003e\n\u003cli\u003eVanhaesebrouck S, Zecic A, Goossens L, Keymeulen A, Garabedian L, De Meulemeester J, et al. Trends in neonatal morbidity and mortality for very low birthweight infants: a 20-year single-center experience. J Matern-Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet. d\u0026eacute;c 2023;36(2):2227311. \u003c/li\u003e\n\u003cli\u003eIsayama T, Lee SK, Mori R, Kusuda S, Fujimura M, Ye XY, et al. Comparison of Mortality and Morbidity of Very Low Birth Weight Infants Between Canada and Japan. PEDIATRICS. 2012;130(4):e957‑65. \u003c/li\u003e\n\u003cli\u003eVaz Ferreira C, Caro J, Villarroel L, Mu\u0026ntilde;oz S, Alvarez P, Flores G, et al. Antenatal exposure to magnesium sulfate and neonatal outcomes in very low birth weight infants: a multicenter study. J Perinatol Off J Calif Perinat Assoc. nov 2024;44(11):1663‑8. \u003c/li\u003e\n\u003cli\u003eCostescu OC, Boia ER, Boia M, Cioboata DM, Doandes FM, Lungu N, et al. The Role of Erythropoietin in Preventing Anemia in the Premature Neonate. Children. d\u0026eacute;c 2023;10(12):1843. \u003c/li\u003e\n\u003cli\u003eCorpeleijn WE, Waard M de, Christmann V, Goudoever JB van, Weide MCJ der, Kooi EMW, et al. Effect of Donor Milk on Severe Infections and Mortality in Very Low-Birth-Weight Infants. JAMA Pediatr. 2016;170(7):654‑654. \u003c/li\u003e\n\u003cli\u003eTarnow-Mordi WO, Abdel-Latif ME, Martin A, Pammi M, Robledo K, Manzoni P, et al. The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial. Lancet Child Adolesc Health. juin 2020;4(6):444‑54. \u003c/li\u003e\n\u003cli\u003eKanic Z, Micetic Turk D, Burja S, Kanic V, Dinevski D. Influence of a combination of probiotics on bacterial infections in very low birthweight newborns. Wien Klin Wochenschr. d\u0026eacute;c 2015;127 Suppl 5:S210-215. \u003c/li\u003e\n\u003cli\u003eGarc\u0026iacute;a-Mu\u0026ntilde;oz Rodrigo F, Fabres JG, Zozaya Nieto C, San Feliciano L, Figueras-Aloy J, Saenz de Pipaon M, et al. Survival and Survival without Major Morbidity Seem to Be Consistently Better throughout Gestational Age in 24- to 30-Week Gestational Age Very-Low-Birth-Weight Female Infants Compared to Males. Neonatology. 2022;119(5):585‑93. \u003c/li\u003e\n\u003cli\u003eVu HD, Dickinson C, Kandasamy Y. Sex Difference in Mortality for Premature and Low Birth Weight Neonates: A Systematic Review. Am J Perinatol. 14 d\u0026eacute;c 2017;35:707‑15. \u003c/li\u003e\n\u003cli\u003ede Almeida MFB, Moreira LMO, Vaz dos Santos RM, Kawakami MD, Anchieta LM, Guinsburg R. Early neonatal deaths with perinatal asphyxia in very low birth weight Brazilian infants. J Perinatol Off J Calif Perinat Assoc. nov 2015;35(11):954‑7. \u003c/li\u003e\n\u003cli\u003eYoun YA, Kim EK, Kim SY. Necrotizing Enterocolitis among Very-Low-Birth-Weight Infants in Korea. J Korean Med Sci. oct 2015;30 Suppl 1(Suppl 1):S75-80. \u003c/li\u003e\n\u003cli\u003eJammeh ML, Adibe OO, Tracy ET, Rice HE, Clark RH, Smith PB, et al. Racial/ethnic differences in necrotizing enterocolitis incidence and outcomes in premature very low birth weight infants. J Perinatol Off J Calif Perinat Assoc. oct 2018;38(10):1386‑90. \u003c/li\u003e\n\u003cli\u003eTing JY, Synnes A, Roberts A, Deshpandey A, Dow K, Yoon EW, et al. Association Between Antibiotic Use and Neonatal Mortality and Morbidities in Very Low-Birth-Weight Infants Without Culture-Proven Sepsis or Necrotizing Enterocolitis. JAMA Pediatr. 1 d\u0026eacute;c 2016;170(12):1181‑7. \u003c/li\u003e\n\u003cli\u003eCantey JB, Anderson KR, Kalagiri RR, Mallett LH. Morbidity and mortality of coagulase-negative staphylococcal sepsis in very-low-birth-weight infants. World J Pediatr WJP. juin 2018;14(3):269‑73.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Infant, Very Low Birth Weight - Mortality – Morbidity-Survival","lastPublishedDoi":"10.21203/rs.3.rs-7754946/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7754946/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAlthough the continuous progress of medical care, Very Low Birth Weight (VLBW) infants still have a high risk of mortality and encounter many morbidities, especially in developing countries. This study aimed to describe mortality and morbidity rates and to identify predictive factors of mortality among VLBW neonates.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003e We conducted an exhaustive cross-sectional study in the neonatal Intensive Care Unit of the Teaching Hospital of Monastir in Tunisia, from January 2019 to December 2022. All VLBW infants were included except those with lethal malformations or who died in the delivery room. Data were retrospectively collected and analyzed using SPSS version 21.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 253 neonates were included with a prevalence of 1.2% among live births. Median gestational age was 30 weeks [25\u0026ndash;37 weeks], and median birth weight was 1280g [685-1490g]. Mortality rate was 13.8%, with a median age at death of 6 days. Main causes of death were nosocomial infections (38.2%), Respiratory Distress Syndrome (20.6%), and perinatal asphyxia (17.7%). Independent predictor factors of mortality included birth weight\u0026thinsp;\u0026lt;\u0026thinsp;1000g, seizure, catheter-related complications, and mechanical ventilation. Non-invasive ventilation was protective. All neonates born more than 32 weeks survived.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eMortality among VLBW infants remains high. Preventing infections, reducing catheter complications, and promoting non-invasive ventilation are key strategies to improve outcomes.\u003c/p\u003e","manuscriptTitle":"Short-term outcomes and predictive factors of mortality among Very Low Birth Weight newborns (\u0026lt; 1500g): cross-sectional study in the Neonatal Intensive Care Unit of Monastir, Tunisia.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-31 10:10:56","doi":"10.21203/rs.3.rs-7754946/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-25T18:30:31+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-01T19:02:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-01T11:20:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-26T18:52:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"63867961752905613840030543057070127168","date":"2025-10-23T12:02:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"221138433703274709792301800768606511420","date":"2025-10-23T06:03:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"286113399838953164260505921722365967332","date":"2025-10-23T02:27:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"236126400439073045079205244852016891940","date":"2025-10-21T12:18:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-21T07:14:26+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-07T12:42:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-07T01:02:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-07T01:01:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2025-09-30T21:15:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d2704167-2f9a-47d1-a3d2-c895df0c2031","owner":[],"postedDate":"October 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-03-25T18:39:35+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-31 10:10:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7754946","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7754946","identity":"rs-7754946","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}