How long does it take to start minimal enteral feeding in preterm Neonates admitted to NICUs in Southern Oromia, Ethiopia?

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Abstract Background The timely initiation of trophic feeding (TF) is crucial for premature newborns, but challenging due to immaturity, respiratory instability, abdominal distension, resource scarcity, and healthcare worker expertise. Moreover, there is a dearth of information on predictors of full trophic feeding time. Therefore, this retrospective cohort study aimed to investigate the time it takes and its predictors to initiate minimal enteral feeding in preterm neonates in Southern Oromia. Method A facility-based retrospective follow up study was conducted among 434 randomly selected preterm neonates admitted to NICU of Bule Hora University Teaching Hospital and Yabello General Hospital from January 1, 2021-December 30, 2022. Data were extracted by a pretested structured checklist, entered into Epidata 3.1 and then transferred to Stata version 17 for analysis. Kaplan Meier survival curve and log rank test were used to estimate survival time and a statistical comparison respectively. Bivariable and multivariable cox proportional hazard model was fitted to identify predictors of time to initiate TF and their outputs are presented using Adjusted Hazard Ratio (AHR) with 95% Confidence Intervals (CIs). Result In our study, the overall incidence density rate (IDR) of initiation of TF was 43.6 per 100 neonates-days of follow-up with a median time to start TF of 2 days and also only 21.93% of newborns started TF on the first day of observation. Furthermore, Neonates born vaginally (AHR: 1.64, 95% CI: 1.26, 2.13), GA of 32 < 34 weeks (AHR: 0.61, CI: 0.46, 0.81), VLBW (AHR = 0.45, CI: (0.34, 0.60), absence of KMC (AHR: 0.59, CI: 0.46, 0.79), absence of sepsis (AHR: 1.76, CI: 1.36, 2.28), absence of hypothermia (AHR: 1.51, CI: 1.19, 1.93) and secondary level of hospital (AHR: 0.78, CI: 0.62, 0.99) were associated with initiation of TF. Conclusion We observed a significant low rate of TF initiation and higher death rate of preterm newborn in our study as compared to the global. Preterm neonates with lower GA, no KMC, and a VLBW are more likely to have a delayed initiation. Our results highlight that, staff training on identifying neonates suitable for TF, and ensuring adequate resources for KMC in all NICU levels should be considered. Moreover, further studies are required to validate these findings and determine the influence on clinical outcomes.
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Anteneh Fikrie, Terefu Yambo, Alo Edin, Miesa Gelchu, Dejene Hailu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4566019/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Feb, 2025 Read the published version in Italian Journal of Pediatrics → Version 1 posted 5 You are reading this latest preprint version Abstract Background The timely initiation of trophic feeding (TF) is crucial for premature newborns, but challenging due to immaturity, respiratory instability, abdominal distension, resource scarcity, and healthcare worker expertise. Moreover, there is a dearth of information on predictors of full trophic feeding time. Therefore, this retrospective cohort study aimed to investigate the time it takes and its predictors to initiate minimal enteral feeding in preterm neonates in Southern Oromia. Method A facility-based retrospective follow up study was conducted among 434 randomly selected preterm neonates admitted to NICU of Bule Hora University Teaching Hospital and Yabello General Hospital from January 1, 2021-December 30, 2022. Data were extracted by a pretested structured checklist, entered into Epidata 3.1 and then transferred to Stata version 17 for analysis. Kaplan Meier survival curve and log rank test were used to estimate survival time and a statistical comparison respectively. Bivariable and multivariable cox proportional hazard model was fitted to identify predictors of time to initiate TF and their outputs are presented using Adjusted Hazard Ratio (AHR) with 95% Confidence Intervals (CIs). Result In our study, the overall incidence density rate (IDR) of initiation of TF was 43.6 per 100 neonates-days of follow-up with a median time to start TF of 2 days and also only 21.93% of newborns started TF on the first day of observation. Furthermore, Neonates born vaginally (AHR: 1.64, 95% CI: 1.26, 2.13), GA of 32 < 34 weeks (AHR: 0.61, CI: 0.46, 0.81), VLBW (AHR = 0.45, CI: (0.34, 0.60), absence of KMC (AHR: 0.59, CI: 0.46, 0.79), absence of sepsis (AHR: 1.76, CI: 1.36, 2.28), absence of hypothermia (AHR: 1.51, CI: 1.19, 1.93) and secondary level of hospital (AHR: 0.78, CI: 0.62, 0.99) were associated with initiation of TF. Conclusion We observed a significant low rate of TF initiation and higher death rate of preterm newborn in our study as compared to the global. Preterm neonates with lower GA, no KMC, and a VLBW are more likely to have a delayed initiation. Our results highlight that, staff training on identifying neonates suitable for TF, and ensuring adequate resources for KMC in all NICU levels should be considered. Moreover, further studies are required to validate these findings and determine the influence on clinical outcomes. Preterm neonates Trophic feeding Predictors Time to initiate Survival analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Background According to World Health Organization (WHO), preterm birth is a birth before 37 completed weeks of gestation ( 1 ). It is a significant global public health concern, accounting for nearly 1 in 10 babies born worldwide ( 2 ). In 2019, 15.22 million neonatal preterm birth incidents occurred globally, with prevalence in Sub-Saharan Africa ranging from 3.4–49.4% ( 3 ). In Ethiopia the prevalence ranges from 10.48–11.4% ( 4 , 5 ). Prematurity increases risks for short- and long-term complications due to underdeveloped gut mobility, microbiome, blood flow, and immunity ( 6 – 8 ). Trophic feeding (TF) also called minimal enteral nutrition, refers to the provision of enteral nutrition without the expectation of full nutritional needs being met, and it is the standard of care in neonatology for preterm neonates in the Neonatal Intensive Care Unit (NICU) ( 9 , 10 ). TF has a positive effect on growth, mortality and common morbidities among preterm neonates ( 11 , 12 ). Around 90% and 40% of preterm and very low birth weight (VLBW) infants experience growth delay due to inadequate enteral feeding initiation ( 8 ). Clinical guidelines suggest the volume of feeding considered trophic for preterm newborns is 10–15 mL/kg/day and should be started within 24–48 hours of birth ( 9 ), but implementation varies globally ( 13 – 15 ). The European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines suggest starting with minimal enteral feeding of 20–25 ml/kg/day at 0.5-1 ml/kg/h, increasing by 20–25% every 24–48 hours ( 16 ). The Ethiopian NICU treatment guideline suggests early (within 24 hrs.) enteral feeding for preterm neonates ( 17 ), however initiating on time remains a challenge ( 18 , 19 ). Meta-analysis evidence revealed that Early TF with volumes up to 24 ml/kg/day introduced before 96 hours of birth ( 20 ). Numerous systematic reviews and meta-analyses claims early TF initiation in high-risk infants is safe, not increasing NEC risk, and leads to improved neonatal feeding tolerance, maintenance of intestinal function during starvation, prevention of intestinal bacterial overgrowth and long-term outcomes for preterm infants ( 12 , 21 , 22 ). Delayed initiation of TF is a global concern in NICUs and has been identified as a significant independent predictor of poor growth among preterm neonates ( 23 ). It has been associated with increasing the risk of nutritional deficits, impaired brain growth, sepsis, feeding intolerance, low weight and poor survival among preterm neonates ( 7 , 22 , 24 ). Studies show significant delays and a median time of 7–13 days for full enteral feeding ( 25 – 27 ). In Africa, only small proportions start minimal feeding early ( 28 – 30 ). Similarly, studies from Ethiopia show significant delays in TF for neonates, with 80–90% not receiving it within 48 hours, 20% receiving it within 24 hours, 29% dying before discharge, and 86.2% experiencing extra uterine growth restriction ( 19 , 31 , 32 ). Therefore further determination of predictors of TF initiation is crucial for successful modification, development, and implementation of appropriate feeding guidelines for premature infants and improving clinical practice ( 18 , 30 , 33 ). Although, previous studies identified several predictors of delayed initiation of minimal enteral feeding in preterm neonates, including physiological immaturity of the GI tract, gestational age, maternal hypertension, cesarean delivery, respiratory distress syndrome, perinatal asphyxia, limited resources and healthcare worker expertise ( 22 , 27 , 34 , 35 ), studies had utilized relatively small sample sizes, and varied definitions of delayed initiation, making it challenging to compare and generalize the findings across different populations ( 28 ). Moreover, the current study considered the impact of NICU practices and protocols between two recourse limited hospitals that were not consistently examined in previous research, Bule Hora University Teaching Hospital and Yabello General Hospitals, both located in peripheral areas and potentially marginalized. Methods and materials Study design and period A facility-based retrospective follow -up study was conducted from January 1, 2021-December 30, 2022. Study area The study was conducted in Bule Hora University Teaching Hospital (BHUTH) and Yabello General Hospital (YGH), Southern Oromia region's largest hospitals. BHUTH located in Bule Hora town, offers various services to 5 million people of West Guji Zone and its surroundings. It has a total of 346 administrative and technical staffs. The services are, includes pediatrics, emergency, delivery, outpatient, inpatient, laboratory, pharmacy, medical, and surgical services. The NICU of the hospital has an approximate of 600 preterm neonate admissions per year ( 36 ). On the other hand, Yabello General Hospital found in Yabello town, provides health services to 926,690 people in the Borena Zone, with an estimated 400 preterm neonate admissions annually in its NICU ( 37 ). Population, Sample size determination and Sampling technique All preterm neonates admitted to the NICUs of Bule Hora University Teaching Hospital and Yabello General Hospital during the specified timeframe (January 1, 2021 - December 30, 2022) were eligible for our study. Records of neonates with incomplete charts, major congenital anomalies that interfere with feeding, those who developed NEC before initiation of enteral feeding and those started breast feeding or TF prior to admission were excluded. We calculated the s ample size using Stata version 17 by considering AHR of 0.74 ( 19 ) two-sided 5% significant level, power of 80% and 20% probability of withdrawing from a study. Then minimum sample size obtained was 476. The total sample size was proportionally allocated to each study hospitals and systematic random sampling technique was used to select study subjects from the list of medical records. Sampling interval (k) was calculated by dividing total population at each hospital for sample size for respective hospitals (k = 2). So, the 2nd medical record number was randomly selected from the sampling frame. Data abstraction tool and quality management The study used a data abstraction checklist to ensure data quality, with a pretest conducted on 5% of preterm neonates at Adola General Hospital. Based on the pretest result, educational level of the mother was removed whereas kangaroo mother care and antibiotic were added to the checklist. The data were extracted by experienced four BSc nurse professionals, with supervision and daily evaluations to ensure completeness and consistency. One-day training was given for data extractors and supervisors regarding data extractions. Study Variables and Operational definitions Our study outcome variable was time to initiate TF, which was determined by subtracting the birth date from the date of TF initiation. Independent variables were neonatal related factors such as birth weight, sex, gestational age, hypothermia, meconium aspiration syndrome, first minute Apgar score, fifth minutes Apgar score, perinatal asphyxia, sepsis, jaundice, hemodynamic instabilities and respiratory distress syndrome; maternal socio-demographic, medical and obstetric related factors such as age of the mother, residence, educational status, having ANC follow up, Premature rupture of membrane (PROM), preeclampsia, mode of delivery, postpartum hemorrhage, place of delivery, parity, gravidity and birth type and health service related factor such as kangaroo mother care, antibiotics, continuous positive air pressure, frequency of order revision and hospital type. Trophic feeding The first minimal enteral feeding to prime the gut regardless of method ( 9 , 38 ). Early trophic feeding A small volume of milk (less than 24 ml/kg/day) provided within 24–48 h of birth to stimulate gastrointestinal motility ( 12 ). Survival time the length of time in days followed starting from birth to the first trophic feeding or censorship. Event initiation of first trophic feeding for preterm neonates. Censored those neonates, who died, transferred or referred before starting trophic feeding or not started at end of follow-up. Follow up time time from birth up to either the study subjects start trophic feeding or censored. Hemodynamic instabilities Patent ductus arteriosus, blood group and RH incompatibility, anemia, polycythemia, bleeding disorders, blood glucose disturbances ( 39 ). Data processing and Analysis Data were entered to Epi-Data version 3.1 and transferred to STATA version 17 for analysis. Descriptive statistics like frequency and percentage were used to describe the socio-demographic characteristics of the mother and the neonate. Continuous data containing variables were summarized with median and interquartile range. Pearson chi square test was used to compare the two groups of the neonate and p-value of < 0.05 was considered statistically significant to declare difference. The Kaplan Meier survival curve and a log-rank test were used to estimate survival time and compare the survival curves of categorical variables respectively. Assumptions of cox proportional hazard were checked by Schoenfeld residual test and graphically. Additionally, −ln(− ln) survival plot were parallel and Kaplan Meier and predicted survival plot were close for all included covariates which indicates proportional hazard assumption fulfillment (Supplementary material). A bi-variable Cox-regression was computed for each predictor variable and a P-value of < 0.25 were used as cut off point to select variables to be entered in to multivariable cox-regression. Accordingly, result of the final model was expressed in terms of adjusted hazard ratio (AHR) with 95% confidence interval and significant association was declared with a p-value less than 0.05 in a multivariable Cox regression model. Finally, result of the study is presented with tables, graphs, and text narrations. Results From a total of 476 randomly selected records of preterm neonates, the data of 411 with complete medical records were extracted with a retrieval rate of 86.34%. Charts of 65 neonates were excluded (41 were due to initiation of breast feeding directly before TF, 20 were incomplete and 4 had congenital anomaly). Maternal clinical and obstetric characteristics The vast majority (83%) of mothers received antenatal care (Table 1 ). The median (IQR) age of mothers of the neonates was 30 ( 24 – 35 ) years. Most births were vaginal (63%) and singletons (81%). Deliveries primarily occurred at healthcare facilities (85%). Most mothers (76%) were multiparous (having given birth before). Figure 1 illustrates 42% of mothers have at least one form of medical or obstetrics complication during their current pregnancy. Preeclampsia (21%) and premature membrane ruptures (18%) were the most frequent complications. Table 1 Clinical and obstetric characteristics of the mothers of preterm neonates admitted to NICU of BHUTH and YGH, 2023 from January 1, 2021-December 30, 2022 (n = 411). Variables Category Frequency Percent (%) Maternal age in years ≤ 19 37 9 20–24 68 16.55 25–29 96 23.36 30–34 97 23.60 ≥ 35 113 27.49 Residence Rural 169 41.12 Urban 242 58.88 ANC follow up Yes 343 83.21 No 69 16.79 Number of ANC (n = 342) 1–3 306 69.3 ≥ 4 105 30.7 Mode of delivery Spontaneous vaginal 260 66 Cesarean section 134 28.87 Instrumental 17 4.13 Place of delivery At home 59 14.36 Health institution 352 85.64 Institutional delivery (n = 352) In born 255 72.44 Out born 97 27.66 Type of current pregnancy Singleton 333 81 Multiple 78 20 Parity Primiparous 100 24.33 Multiparous 311 75.77 Gravidity Primigravida 94 22.87 Multigravida 277 67.40 Grand multigravida 40 9.73 Neonatal baseline characteristics and service delivery factors Both sexes were almost equally represented with a male to female ratio of 0.97 (Table 2 ). The median (IQR) weight of the neonates was 1600 (1400–2000) grams. Minimum and maximum gestational ages at birth were 28 and 36 weeks, respectively. Almost a quarter, 24.33% of the neonates had 1st minute APGAR score of less than 7. Additionally, 41.85% and 93.43% of admitted neonates were small for gestational age (SGA) and given antibiotics respectively. As Ninety-two per cent of preterm neonates have at least one form of medical complication ( Fig. 2 ) . Hypothermia (43.80%) and jaundice (13.14%) were identified as the highest and lowest complications occurred respectively. Table 2 Neonatal baseline characteristics and service delivery factors of preterm neonates admitted from January 2021-December 2022 to NICU of BHUTH and YGH, 2023(n = 411). Variable Category Frequency Percent (%) Sex of the neonate Female 208 50.61 Male 203 49.39 Birth weight (BW) < 2.5kg 227 55.23 < 1.5kg 184 44.77 Gestational age (GA) in weeks 34 to < 37 185 45.01 32 to < 34 121 29.44 28 to < 32 105 25.55 1st minite APGAR score < 7 100 24.33 ≥ 7 311 75.67 5th minute APGAR score < 7 88 21.41 ≥ 7 323 78.59 Weight for gestational age Small 172 41.85 Appropriate 239 58.15 Kangaroo mother care Yes 215 52.31 No 196 47.69 Antibiotic Yes 384 93.43 No 27 6.57 Continuous Positive Airway Pressure (CPAP) Yes 37 9 No 374 91 Location of NICU neonates admitted YGH 199 48.42 BHUTH 212 51.58 Frequency of order revision 24 hours 93 22.63 Time to initiate TF and overall survival function of preterm neonates The overall incidence rate of TF was calculated using person-days of follow up as a denominator for the entire cohort. Accordingly, a total of 411 premature neonates were followed for a total of 690 neonate-days of observation with a minimum of 1 and maximum of 6 days. During the follow up period 301 (73.2%), 78 (19%), 28 (6.8%), and 4 (1%) premature neonates started TF, died, referred and left against medical advice, respectively. Our study's result indicates that the overall incidence density of TF initiation was reported as 43.6 per 100 neonate-days. Moreover, the median (IQR) time to initiate TF was found to be 2 ( 1 – 4 ) days. Additionally, in the first day (24 hours), only 66 out of 411 neonates (16.6%) initiated TF (Table 3 ). By the end of 6 days (144 hours), only 24 neonates remained, with 14 starting TF, 10 being censored, and the survival probability dropping to 0.0359 (95% CI: 0.01 to 0.074). Table 3 The life table analysis of preterm neonates to start TF among preterm neonates admitted from January 2021-December, 2022 to NICU of BHUTH an YGH, 2023 (n = 411). Time interval Total beginning Started Trophic Feeding Censored Survival probability 95%CI of survival probability 0–1 411 66 28 0.8338 (0.79, 0.87) 1–2 317 110 25 0.5326 (0.48, 0.58) 2–3 182 49 22 0.3800 (0.33, 0.43) 3–4 111 42 13 0.2272 (0.18, 0.27) 4–5 56 20 12 0.1363 (0.09, 0.18) 5–6 24 14 10 0.0359 (0.01, 0.074) Comparison of survivorship functions among different categorical variables. Kaplan-Meier curves (KMc) constructed to compare the overall survival patterns over time for between different groups. Similarly, log-rank test used in conjunction with KM curves to assess if the observed differences in survival between groups were statistically significant. Preterm neonates born to mothers with APH exhibited a significantly later onset of TF compared to those born to mothers without APH ( Fig. 3 ). Likewise, the median time to TF commencement was statistically significant (log-rank test = 12.79, P < 0.001) (Table 4 ). Neonates with sepsis experienced a significantly delayed TF initiation compared to those without sepsis ( Fig. 4 ). In a similar vein, Table 3 shows that a median time of 2 days for preterm neonates and 3 days for those with sepsis was significantly different (Log-rank test = 21.87, P < 0.001). Table 4 Median survival time and log rank test of equality of survivorship to start TF among preterm neonates admitted from January 2021-December 2022 to NICU of BHUTH and YGH, 2023 (n = 411). Variables Median survival time in days (95% CI) Log rank test χ 2 p-value PROM Yes 3 ( 2 , 4 ) 6.58 0.0103 No 2 ( 2 , 3 ) APH Yes 5 ( 3 , 6 ) 12.79 0.0003 No 2 ( 2 , 3 ) Mode of delivery SVD 2 ( 2 , 2 ) 17.39 0.0001 CS 3 ( 3 , 4 ) Maternal HIV/AIDS Yes 4 (2, ) 8.46 0.0036 No 2 ( 2 , 3 ) Birth weight < 1500 3 ( 2 , 3 ) 5.48 0.0192 ≥ 1500 2 ( 2 , 2 ) Gestational age < 34 3 ( 2 , 3 ) 7.79 0.0052 ≥ 34 2 ( 2 , 2 ) Kangaroo mother care Yes 2 ( 2 , 2 ) 17.55 0.0001 No 3 ( 2 , 4 ) Hypothermia Yes 3 ( 2 , 3 ) 11.15 0.0008 No 2 ( 1 , 2 ) Sepsis Yes 3 ( 3 , 4 ) 21.87 0.0001 No 2 ( 2 , 2 ) Level of health care NICU located 2 0 (YGH) 2 (1.5, 2.5) 3 0 (BHUTRH) 3 (2.68, 3.31) Key: 2 o : Secondary; 3 o : Tertiary Predictors of time to initiate trophic feeding among preterm neonates In order to analyze the association between independent variables and time to initiate TF, first bi-variable cox regression was performed. Those variables with p-value of < 0.25 in bi-variable cox regression were entered in to multivariable cox regression for adjusting the potential confounding variables. Accordingly, in Table 5 , the identified significant predictors influencing the time to initiation of TF among preterm neonates at p-value of < 0.05 are displayed. Table 5 Multivariable cox-proportional hazard regression on predictors of time to initiate TF among preterm neonates admitted from January 2021-December, 2022 to NICU of BHUTH and YGH, 2023 (n = 411). Predictor variables Trophic Feeding CHR(95% CI) AHR(95% CI) Started Censored PROM No 243 94 1.34 (1.003,1.79) 1.16 (0.85,1.57) Yes 58 16 1 1 Mode of delivery Operative 92 59 1 1 SVD 209 51 1.43(1.12, 1.83) 1.64 (1.26, 2.13)*** Preeclampsia No 243 83 1.34 (1.005, 1.78) 1.27 (0.94, 1.72) Yes 58 27 1 1 APH No 282 90 1.93 (1.21, 3.08) 1.63 (0.98, 2.71) Yes 19 20 1 1 Gestational age 34 to < 37 148 37 1 1 32 to < 34 83 38 0.71 (0.54,0.93) 0.61 (0.46,0.81)** 28 to < 32 70 35 0.77 (0.58, 1.02) 0.92 (0.67,1.25) Birth weight (gram) < 1500 113 71 0.77 (0.59, 1.00) 0.45 (0.34, 0.60)*** ≥ 1500 188 39 1 1 KMC No 123 73 0.69(0.54, 0.87) 0.59 (0.46, 0.79)*** Yes 178 37 1 1 Maternal HIV/AIDS No 281 98 1.64 (1.04,2.59) 1.50 (0.94,2.39) Yes 20 12 1 1 Neonatal sepsis No 208 48 1.58 (1.23, 2.02) 1.76 (1.36, 2.28)*** Yes 93 62 1 1 Hypothermia No 179 52 1.37 (1.09, 1.74) 1.51 (1.19, 1.93)** Yes 122 58 1 1 Level of hospital 2 0 (YGH) 137 62 0.76 (0.61, 0.96) 0.78 (0.62, 0.99)* 3 0 (BHTH) 164 48 1 1 Note : 2 0 : secondary, 3 0 : Tertiary; *statistically significant p-value < 0.05, **statistically significant p-value < 0.01, ***statistically significant p-value < 0.001. CHR-crude hazard ratio, AHR-adjusted hazard ratio, SVD-Spontaneous vaginal delivery, CS- Cesarean section, APH-Antepartum hemorrhage, WFGA-Weight for gestational age, KMC-Kangaroo mother care, CI-confidence interval. Notably, neonates born vaginally were 64% more likely to initiate TF sooner compared to those born by cesarean section (AHR: 1.64, 95% CI: 1.26, 2.13). Preterm neonates between 32 and 34 weeks gestation had a delayed initiation of TF compared to their more mature counterparts (≥ 34 weeks) (AHR: 0.61, CI: 0.46, 0.81). Additionally, absence of kangaroo mother care was associated with a 41% reduced likelihood of earlier TF initiation (AHR: 0.59, CI: 0.46, 0.79). Likewise, a very LBW ( 1500g) (AHR = 0.45 (0.34, 0.60). Interestingly, the absence of sepsis was also a significant predictor, with neonates without sepsis being 76% more likely to initiate TF compared to those with infection (AHR: 1.76, CI: 1.36, 2.28). Furthermore, the absence of hypothermia was associated with a 51% increased likelihood of earlier TF initiation (AHR: 1.51, CI: 1.19, 1.93). Finally, the level of hospital (YGH-level 2) was associated with a slight delay in initiating TF (AHR: 0.78, CI: 0.62, 0.99). Discussion Our study's objectives were to ascertain when TF was started and its determinants in preterm newborns hospitalized to Yabello General Hospital and Bule Hora University Teaching Hospital's NICU between January 1, 2022, and September 30, 2022. As a result, of the 411 neonates observed on the first day of follow-up, 21.93% began TF, and 28 were censored. However, only 24 were left at the end of the five-day follow-up, with 14 of them having started TF. The overall incidence density in our sample was 43.6 per 100 neonate days. This means, out of every 100 days that newborn babies were observed in our study, TF was started in an average of 43.6 of those days. The median (IQR) time to TF onset of was 2 ( 1 – 4 ) days. Moreover, he study revealed a significant increase in preterm neonatal mortality in Ethiopia, with 113.04 deaths per 1000 neonate-days, a significant increase from previous research. GA (> 34 weeks), SVD, the absence of sepsis, and the absence of hypothermia increase the probability of early initiation of TF by 64%, 76%, and 51%, respectively. Conversely, it was discovered that delayed TF start was caused by BW (< 1500 kg), lack of kangaroo mother care, and being admitted to a level-2 hospital. In our study, we found that only 21.93% of preterm neonates initiated feeding within the first 24 hours of birth, indicating that many did not start within this optimal timeframe. The study's findings are lower than previous studies in Portugal 44% ( 40 ), Tuscany Italy (74.1%) ( 41 ), Iran (36%) ( 42 ), Nigeria and Kenya 48% ( 28 ), New Zealand (60%) ( 23 ), Addis Ababa (29.9%) ( 32 ) and Amhara, Northwest Ethiopia (24.76%) ( 19 ). The discrepancy may be due to differences in service quality, and availability of specialized facilities, milk banks, study period length, sample size, and design between the studies. Moreover, nearly half, (46.74%) of preterm neonates initiated TF feeding within 48 hours of birth. This is comparable with a study conducted in Addis Ababa, Ethiopia (48.2%) ( 32 ). However, it is lower than the findings from Nigerian Special Care Baby Unit (66.7%) ( 43 ), Iran (63.2%) ( 42 ), Uganda rural hospitals (80%) ( 30 ) and New Zealand (80%) ( 23 ). This highlights a significant delay in initiating TF among preterm neonates and creates concerns about high neonatal mortality as evidenced by our study where, over 50% of the neonate died within the first 48 hours of life. This could be because of their initial treacherous condition. The result of this study regarding incidence density of TF is lower than the result of a follow up study conducted in northern Ethiopia ( 19 ), where the incidence density of starting TF was 48 per 100 neonate-days. Moreover, the median (IQR) time of starting TF found in our study 2 (IQR: 1–4) days is slightly higher than the result of a follow up study conducted in China ( 44 ) and a retrospective study in New Zealand ( 23 ) which had a similar median time of 1 day. This discrepancy might be due to difference in service delivery quality, hospital level, having well-equipped institution, sample size and study settings. However, consistent with a longitudinal study in Ethiopia in which median time to start TF was less than 2 days ( 19 ) and a multicenter observational follow up study in Nigeria and Kenya ( 35 ), which might be due to similarity in study design and characteristics of study subjects. This implies that the presence of a significant delay to initiate TF for studied preterm neonates. Preterm neonatal mortality (NMR) was found to be surprisingly common in our study. We found an astounding 113.04 deaths per 1000 neonate-days, a significant increase above earlier research done in various parts of Ethiopia. From 27 per 1000 neonate-days in southern Ethiopia ( 45 ), 29.438 per 1000 neonate-days in Addis Ababa, Central Ethiopia ( 46 ) and to 75.63 per 1000 neonate-days in northwestern Ethiopia ( 47 ), these previous investigations revealed substantially lower fatality rates. The NMR of 45.15 per 1000 neonate-days was reported in a study conducted in Hawassa City, Ethiopia ( 25 ), which is geographically similar to our study area. This is noteworthy. Even the neighboring African country, Burkina Faso had a much lower rate, 1.93 deaths per 1000 person-days ( 48 ). The study's unexpected high NMR result led to a potential explanation of a low proportion of neonates initiating TF early in their lives. Previous research suggests that preterm neonates who don't receive TF early are more susceptible to death ( 46 ). Studies have shown that early TF initiation offers several benefits – it reduces the length of hospital stays, lowers infection rates, and promotes gut development ( 22 ). Conversely, a delay in starting TF might hinder the maturation of the gut, leading to a weakened immune system ( 49 , 50 ). This, in turn, could significantly increase the risk of complications like Necrotizing Enterocolitis (NEC) and various infections, ultimately contributing to higher neonatal mortality ( 51 ). Therefore, we strongly suggest that, in particular, for susceptible groups such as preterm newborns, targeted interventions encouraging early TF initiation could drastically lower NMR rates and increase survival rates. In this study, the chance of starting TF on time was 55% reduced among a very low birth weight ( 1500gm. This finding is in line with the results of retrospective longitudinal a study in China ( 44 ), a retrospective study in New Zealand ( 23 ) and a multicenter prospective study conducted in Ethiopia ( 19 ). This might be due to perceived under-development of organs and low readiness to enteral feeding of preterm neonates with lower birth weight. However in contrast to this, guidelines on feeding of very low birth weight infants recommend early initiation of TF within 1 day after birth, also for this group of preterm neonates ( 9 ). This result highlights the importance of individualized care plans based on birth weight in order to insure early TF for VLBW preterm neonates. Among preterm neonates with a gestational age of less than 34 weeks, there was a statistically significant 39% reduction in the likelihood of initiating TF in comparison to neonates with a gestational age of 34 weeks or more. This result is consistent with findings of observational prospective follow up study in Italy ( 41 ), retrospective follow up study in China ( 44 ), a cross sectional study carried out in two of African countries ( 28 ), a multicenter prospective study conducted in Ethiopia ( 18 ), prospective follow up study conducted in northern Ethiopia ( 19 ) and cross sectional study in Spain ( 15 ), which revealed delayed commencement of TF among newborns with lower gestational age. This might be due to lack of intestinal maturation, anxiety of feeding resistance, and perceived danger of NEC, preterm neonates born before 34 weeks of pregnancy may have gastrointestinal issues. This implies that early identification and support of lower gestational age preterm neonates may improve the time to initiate TF among this group of preterm neonates. The study found that preterm neonates delivered through spontaneous vaginal delivery had a 64% higher likelihood of starting TF compared to those delivered through CS, possibly due to delayed breast milk provision. The study's findings align with a multicenter prospective follow-up conducted in northern Ethiopia ( 19 ), prospective follow-up conducted in Addis Ababa, Ethiopia ( 32 ), and Italy( 27 ). This might be because of the reason that newborn's post-delivery needs may require additional monitoring and assistance, while the mother's recovery from the surgery may take longer. The result implies that preterm neonates delivered with CS are at risk of experiencing delayed initiation of TF and related complications. Thus, the healthcare providers must closely monitor both mothers and babies post-delivery and initiate enteral feeding as soon as the baby is stable and ready. However, this finding is in contrast with a result of observational retrospective follow up study conducted in China which revealed lack of significant association of delivery mode and time to initiate enteral feeding ( 44 ). This discrepancy might be due to difference in characteristics of studied subjects, sample size and study setup. WHO recommended KMC for preterm or low-birth-weight infants, starting in healthcare facilities or at home, and lasting 8–24 hours daily ( 52 ). In line with this evidence, in our study, absence of KMC was associated with a 41% reduced likelihood of earlier TF initiation as compared to those with the care. Similar to this finding, a retrospective follow up study in Turkiye has identified KMC as a main factor to improve enteral feeding skills among preterm neonates ( 53 ). Moreover, a prospective cohort study done in a teaching hospital in India identified that early KMC was safe and associated with reduced time to full feeds (TFF) in preterm neonates ( 54 ). A meta-analysis of randomized controlled trial studies reported that KMC encourages early breastfeeding initiation among preterm and low birth weight infants ( 55 ). This implies that KMC is a gentle, effective method for preterm infants, promoting their health and well-being by allowing early discharge and avoiding agitation in busy wards ( 56 ). On the other hand, preterm neonates without hypothermia had a 51% higher hazard of starting TF when compared to those with hypothermia. This is line with a study conducted in Kuala Lumpur Maternity Hospital ( 57 ). This might be due to the fact that most preterm neonates with hypothermia often receive radiant warmer treatment and stay separated from mothers, making early enteral feeding unsuitable. This implies the significance of effective temperature regulation and thermal management strategies in the care of preterm neonates to facilitate timely initiation of TF. In this study, the hazard of starting TF was 76% increased among premature neonates without sepsis as compared to those with sepsis. This finding is supported with a result of a retrospective study conducted in Kaplan medical center, Israel ( 58 ), Addis Ababa, Ethiopia ( 32 ), and Maharashtra, India ( 59 ). This similarity might be due to the fact that sepsis can cause decreased gut motility, increased risk of NEC ( 60 ), and damage the gut lining ( 61 ), making it difficult for neonates to tolerate enteral feeding. Thus, the healthcare providers may delay TF initiation to control infection, reduce NEC risk, and minimize gut permeability. However in contrast to this, guideline on TF does not consider sepsis as contraindication of TF among premature infants and recommends enteral feeding to be initiated early for this group of preterm infants ( 9 ). The result implies early prevention and treatment of sepsis among preterm neonates might support timely initiation of TF. Our study revealed inconsistency in how TF is initiated for preterm neonates across different healthcare levels. We observed a surprising trend – neonates admitted to the secondary-level hospital (YGH) were 22% less likely to receive TF compared to those in the tertiary hospital (BHTRH). This finding is particularly concerning, as timely initiation of TF is crucial for the survival and development of preterm infants. Similar trends were recognized in prior research conducted in Addis Ababa, Ethiopia ( 32 ), highlighting a potential issue within the Ethiopian healthcare system. Additionally, studies across geographically distinct locations like Nigeria and Kenya have reported similar disparities ( 28 , 35 ). This observed similarities suggests a concerning possibility that preterm neonates in less-resourced facilities may face systemic disadvantages when it comes to accessing essential and life-saving interventions like TF. Moreover, the secondary hospitals might have lack of resources, trained personnel, and logistical challenges. Therefore, our study highlights the need for a comprehensive investigation into the disparity in access to TF across healthcare levels, including capacity building, resource allocation, and logistical processes. To the best of our knowledge our study is among few in Ethiopia conducted to determine the time to initiate trophic feeding, involving advanced statistical analysis. However, due to retrospective nature, incomplete data was excluded, potentially introducing selection bias. The data was collected from secondary sources, potentially missing important predictors like nurse-patient ratio and breast milk availability. Conclusion Our study highlights significant opportunities to improve early trophic feeding (TF) practices for preterm neonates. Only 16.6% initiated TF within the first 24 hours, suggesting a gap between current practice and optimal timing. Additionally, disparities exist across healthcare levels, with neonates in secondary-level hospitals 22% less likely to receive TF compared to those in tertiary centers. Factors promoting early TF initiation include: Vaginal delivery (SVD), Absence of sepsis or hypothermia and Kangaroo mother care. Conversely, early TF initiation is hindered by: Lower gestational age (32–34 weeks), Lower birth weight (< 1500g), Lack of kangaroo mother care and Admission to a secondary hospital. Based on these findings, we propose the following feasible and practical recommendations: Implement clear guidelines for initiating TF based on gestational age, birth weight, and clinical condition, ensuring consistency across healthcare levels. Provide training and resources to healthcare professionals at secondary facilities to ensure they feel confident initiating TF for eligible preterm neonates. Encourage and support kangaroo mother care practices for all eligible preterm neonates, recognizing its positive impact on TF initiation. Ensure adequate staffing and equipment’s are available at both secondary and tertiary hospitals to support early TF implementation. Declarations Ethics approval and consent to participate Ethical clearance was obtained from the Institutional Research Ethics Review Committee (IERC) of Institute of Health (IOH), Bule Hora University, ensuring the study adheres to ethical research principles. The study involved the secondary analysis of data from preterm neonates and their mother’s medical records at Bule Hora University Teaching Hospital (BHUTH) and Yabello General Hospital (YGH) specifically from the NICU. Following IERC approval, submissions were made to the administrative offices of both BHUTH and YGH for their respective approvals. Since the study was a retrospective study, informed consent would not seek from individual participants. However, we obtained written permissionfrom the heads of the NICU at each hospital to access the medical records for research purposes. This has been approved by the IOH- IRERC. Data were anonymized, stored securely, and only accessible to the principal investigators to maintain participant confidentiality and minimize identification risks. Consent for publication Not applicable. Availability of data and materials For those who are interested; the datasets of this study could be accessed from the corresponding author on reasonable request Competing Interests The author(s) declared no potential competing of interest with respect to the research, authorship, and/or publication of this article. Funding: Bule Hora University has supported the study financially. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript Author Contributions AF, TY: Conceptualization, Methodology, Data analysis, Writing - Original Draft, Writing - Review & Editing, interpretation of data and approved the final manuscript. AE, MG: Data collection, Investigation, Writing - Review & Editing, interpretation of data and approved the final manuscript. DH, MS: Supervision, Project administration, Writing - Review & Editing, interpretation of data and approved the final manuscript. All authors have made substantial contributions to this manuscript. Acknowledgments We acknowledge the financial support provided by Bule Hora University, Research Ethics, Dissemination and Publication Directorate, which significantly facilitated to conduct our study. Our sincere gratitude extends to the chief administrators of Bule Hora University Teaching Hospital and Yabello General Hospital, as well as the respective NICU department heads, for their invaluable assistance and unwavering support in facilitating data extraction process. Finally, we commend the dedication and professionalism of our data extraction team and supervisors, whose meticulous work ensured the quality and integrity of the extracted data. References World Health Organization (WHO). Preterm birth: 2021. https://www.who.int/news-room/fact-sheets/detail/preterm-birth. World Health Organization (WHO). Preterm birth 10 May 2023 [cited 2024 April 14]. 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Risk factors of necrotizing enterocolitis in neonates with sepsis: A retrospective case-control study. International Journal of Immunopathology and Pharmacology. 2020;34:2058738420963818. Cotten CM. Modifiable risk factors in necrotizing enterocolitis. Clinics in Perinatology. 2019;46(1):129-43. Supplementary Files Subfile1CoxProportionalhazardassumption.docx Cite Share Download PDF Status: Published Journal Publication published 07 Feb, 2025 Read the published version in Italian Journal of Pediatrics → Version 1 posted Editorial decision: Minor revision 15 Sep, 2024 Reviewers agreed at journal 29 Jun, 2024 Reviewers invited by journal 29 Jun, 2024 Editor assigned by journal 14 Jun, 2024 First submitted to journal 14 Jun, 2024 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. 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(n=411).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4566019/v1/7f1fd7525a9f2613c6da7c3f.jpg"},{"id":60852761,"identity":"868c686d-091e-4aa9-9999-56cee24cb513","added_by":"auto","created_at":"2024-07-22 21:12:41","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":30933,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier survival estimate to start TF based on maternal APH of preterm neonates admitted from January 2021-December 2022 to NICU of BHUTH and YGH, 2023 (n=411).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4566019/v1/640bae7a740c1464b029b977.jpg"},{"id":60852762,"identity":"2a80a067-19d9-4342-9382-989874b414d4","added_by":"auto","created_at":"2024-07-22 21:12:41","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":28995,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier survival estimate to start TF based on sepsis of preterm neonates admitted from January 2021-December 2022 to NICU of BHUTH and YGH, 2023 (n=411).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4566019/v1/149683f8f2b580259bf99b42.jpg"},{"id":75930789,"identity":"d645a086-2a0d-4d63-9924-cb0ba38c3151","added_by":"auto","created_at":"2025-02-10 16:13:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1621897,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4566019/v1/ab669298-31cb-4486-8b31-8909a9e99217.pdf"},{"id":60852763,"identity":"1aa9d936-7695-4d35-b710-19840153c737","added_by":"auto","created_at":"2024-07-22 21:12:41","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":172097,"visible":true,"origin":"","legend":"","description":"","filename":"Subfile1CoxProportionalhazardassumption.docx","url":"https://assets-eu.researchsquare.com/files/rs-4566019/v1/92833c4d52177aaf3d0af469.docx"}],"financialInterests":"","formattedTitle":"How long does it take to start minimal enteral feeding in preterm Neonates admitted to NICUs in Southern Oromia, Ethiopia?","fulltext":[{"header":"Background","content":"\u003cp\u003eAccording to World Health Organization (WHO), preterm birth is a birth before 37 completed weeks of gestation (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It is a significant global public health concern, accounting for nearly 1 in 10 babies born worldwide (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). In 2019, 15.22\u0026nbsp;million neonatal preterm birth incidents occurred globally, with prevalence in Sub-Saharan Africa ranging from 3.4\u0026ndash;49.4% (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). In Ethiopia the prevalence ranges from 10.48\u0026ndash;11.4% (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Prematurity increases risks for short- and long-term complications due to underdeveloped gut mobility, microbiome, blood flow, and immunity (\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Trophic feeding (TF) also called minimal enteral nutrition, refers to the provision of enteral nutrition without the expectation of full nutritional needs being met, and it is the standard of care in neonatology for preterm neonates in the Neonatal Intensive Care Unit (NICU) (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). TF has a positive effect on growth, mortality and common morbidities among preterm neonates (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Around 90% and 40% of preterm and very low birth weight (VLBW) infants experience growth delay due to inadequate enteral feeding initiation (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eClinical guidelines suggest the volume of feeding considered trophic for preterm newborns is 10\u0026ndash;15 mL/kg/day and should be started within 24\u0026ndash;48 hours of birth (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), but implementation varies globally (\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines suggest starting with minimal enteral feeding of 20\u0026ndash;25 ml/kg/day at 0.5-1 ml/kg/h, increasing by 20\u0026ndash;25% every 24\u0026ndash;48 hours (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). The Ethiopian NICU treatment guideline suggests early (within 24 hrs.) enteral feeding for preterm neonates (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), however initiating on time remains a challenge (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Meta-analysis evidence revealed that Early TF with volumes up to 24 ml/kg/day introduced before 96 hours of birth (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Numerous systematic reviews and meta-analyses claims early TF initiation in high-risk infants is safe, not increasing NEC risk, and leads to improved neonatal feeding tolerance, maintenance of intestinal function during starvation, prevention of intestinal bacterial overgrowth and long-term outcomes for preterm infants (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDelayed initiation of TF is a global concern in NICUs and has been identified as a significant independent predictor of poor growth among preterm neonates (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). It has been associated with increasing the risk of nutritional deficits, impaired brain growth, sepsis, feeding intolerance, low weight and poor survival among preterm neonates (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Studies show significant delays and a median time of 7\u0026ndash;13 days for full enteral feeding (\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). In Africa, only small proportions start minimal feeding early (\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Similarly, studies from Ethiopia show significant delays in TF for neonates, with 80\u0026ndash;90% not receiving it within 48 hours, 20% receiving it within 24 hours, 29% dying before discharge, and 86.2% experiencing extra uterine growth restriction (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Therefore further determination of predictors of TF initiation is crucial for successful modification, development, and implementation of appropriate feeding guidelines for premature infants and improving clinical practice (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough, previous studies identified several predictors of delayed initiation of minimal enteral feeding in preterm neonates, including physiological immaturity of the GI tract, gestational age, maternal hypertension, cesarean delivery, respiratory distress syndrome, perinatal asphyxia, limited resources and healthcare worker expertise (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e), studies had utilized relatively small sample sizes, and varied definitions of delayed initiation, making it challenging to compare and generalize the findings across different populations (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Moreover, the current study considered the impact of NICU practices and protocols between two recourse limited hospitals that were not consistently examined in previous research, Bule Hora University Teaching Hospital and Yabello General Hospitals, both located in peripheral areas and potentially marginalized.\u003c/p\u003e"},{"header":"Methods and materials","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and period\u003c/h2\u003e \u003cp\u003eA facility-based retrospective follow -up study was conducted from January 1, 2021-December 30, 2022.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy area\u003c/h2\u003e \u003cp\u003eThe study was conducted in Bule Hora University Teaching Hospital (BHUTH) and Yabello General Hospital (YGH), Southern Oromia region's largest hospitals. BHUTH located in Bule Hora town, offers various services to 5\u0026nbsp;million people of West Guji Zone and its surroundings. It has a total of 346 administrative and technical staffs. The services are, includes pediatrics, emergency, delivery, outpatient, inpatient, laboratory, pharmacy, medical, and surgical services. The NICU of the hospital has an approximate of 600 preterm neonate admissions per year (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). On the other hand, Yabello General Hospital found in Yabello town, provides health services to 926,690 people in the Borena Zone, with an estimated 400 preterm neonate admissions annually in its NICU (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePopulation, Sample size determination and Sampling technique\u003c/h2\u003e \u003cp\u003eAll preterm neonates admitted to the NICUs of Bule Hora University Teaching Hospital and Yabello General Hospital during the specified timeframe (January 1, 2021 - December 30, 2022) were eligible for our study. Records of neonates with incomplete charts, major congenital anomalies that interfere with feeding, those who developed NEC before initiation of enteral feeding and those started breast feeding or TF prior to admission were excluded. We calculated the \u003cb\u003es\u003c/b\u003eample size using Stata version 17 by considering AHR of 0.74 (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) two-sided 5% significant level, power of 80% and 20% probability of withdrawing from a study. Then minimum sample size obtained was 476. The total sample size was proportionally allocated to each study hospitals and systematic random sampling technique was used to select study subjects from the list of medical records. Sampling interval (k) was calculated by dividing total population at each hospital for sample size for respective hospitals (k\u0026thinsp;=\u0026thinsp;2). So, the 2nd medical record number was randomly selected from the sampling frame.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData abstraction tool and quality management\u003c/h2\u003e \u003cp\u003eThe study used a data abstraction checklist to ensure data quality, with a pretest conducted on 5% of preterm neonates at Adola General Hospital. Based on the pretest result, educational level of the mother was removed whereas kangaroo mother care and antibiotic were added to the checklist. The data were extracted by experienced four BSc nurse professionals, with supervision and daily evaluations to ensure completeness and consistency. One-day training was given for data extractors and supervisors regarding data extractions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStudy Variables and Operational definitions\u003c/h2\u003e \u003cp\u003eOur study outcome variable was time to initiate TF, which was determined by subtracting the birth date from the date of TF initiation. Independent variables were neonatal related factors such as birth weight, sex, gestational age, hypothermia, meconium aspiration syndrome, first minute Apgar score, fifth minutes Apgar score, perinatal asphyxia, sepsis, jaundice, hemodynamic instabilities and respiratory distress syndrome; maternal socio-demographic, medical and obstetric related factors such as age of the mother, residence, educational status, having ANC follow up, Premature rupture of membrane (PROM), preeclampsia, mode of delivery, postpartum hemorrhage, place of delivery, parity, gravidity and birth type and health service related factor such as kangaroo mother care, antibiotics, continuous positive air pressure, frequency of order revision and hospital type.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eTrophic feeding\u003c/strong\u003e \u003cp\u003eThe first minimal enteral feeding to prime the gut regardless of method (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEarly trophic feeding\u003c/strong\u003e \u003cp\u003eA small volume of milk (less than 24 ml/kg/day) provided within 24\u0026ndash;48 h of birth to stimulate gastrointestinal motility (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eSurvival time\u003c/strong\u003e \u003cp\u003ethe length of time in days followed starting from birth to the first trophic feeding or censorship.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEvent\u003c/strong\u003e \u003cp\u003einitiation of first trophic feeding for preterm neonates.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCensored\u003c/strong\u003e \u003cp\u003ethose neonates, who died, transferred or referred before starting trophic feeding or not started at end of follow-up.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eFollow up time\u003c/strong\u003e \u003cp\u003etime from birth up to either the study subjects start trophic feeding or censored.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eHemodynamic instabilities\u003c/strong\u003e \u003cp\u003ePatent ductus arteriosus, blood group and RH incompatibility, anemia, polycythemia, bleeding disorders, blood glucose disturbances (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e).\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eData processing and Analysis\u003c/h2\u003e \u003cp\u003eData were entered to Epi-Data version 3.1 and transferred to STATA version 17 for analysis. Descriptive statistics like frequency and percentage were used to describe the socio-demographic characteristics of the mother and the neonate. Continuous data containing variables were summarized with median and interquartile range. Pearson chi square test was used to compare the two groups of the neonate and p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant to declare difference. The Kaplan Meier survival curve and a log-rank test were used to estimate survival time and compare the survival curves of categorical variables respectively. Assumptions of cox proportional hazard were checked by Schoenfeld residual test and graphically. Additionally, \u0026minus;ln(\u0026minus;\u0026thinsp;ln) survival plot were parallel and Kaplan Meier and predicted survival plot were close for all included covariates which indicates proportional hazard assumption fulfillment (Supplementary material). A bi-variable Cox-regression was computed for each predictor variable and a P-value of \u0026lt;\u0026thinsp;0.25 were used as cut off point to select variables to be entered in to multivariable cox-regression. Accordingly, result of the final model was expressed in terms of adjusted hazard ratio (AHR) with 95% confidence interval and significant association was declared with a p-value less than 0.05 in a multivariable Cox regression model. Finally, result of the study is presented with tables, graphs, and text narrations.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eFrom a total of 476 randomly selected records of preterm neonates, the data of 411 with complete medical records were extracted with a retrieval rate of 86.34%. Charts of 65 neonates were excluded (41 were due to initiation of breast feeding directly before TF, 20 were incomplete and 4 had congenital anomaly).\u003c/p\u003e\n\u003ch3\u003eMaternal clinical and obstetric characteristics\u003c/h3\u003e\n\u003cp\u003eThe vast majority (83%) of mothers received antenatal care (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The median (IQR) age of mothers of the neonates was 30 (\u003cspan additionalcitationids=\"CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e) years. Most births were vaginal (63%) and singletons (81%). Deliveries primarily occurred at healthcare facilities (85%). Most mothers (76%) were multiparous (having given birth before). Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates 42% of mothers have at least one form of medical or obstetrics complication during their current pregnancy. Preeclampsia (21%) and premature membrane ruptures (18%) were the most frequent complications.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical and obstetric characteristics of the mothers of preterm neonates admitted to NICU of BHUTH and YGH, 2023 from January 1, 2021-December 30, 2022 (n\u0026thinsp;=\u0026thinsp;411).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVariables Category\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercent (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eMaternal age in years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u0026ndash;24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u0026ndash;29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u0026ndash;34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eResidence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRural\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrban\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e242\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eANC follow up\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e343\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.79\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNumber of ANC (n\u0026thinsp;=\u0026thinsp;342)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eMode of delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpontaneous vaginal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCesarean section\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInstrumental\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePlace of delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAt home\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHealth institution\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e352\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eInstitutional delivery\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;352)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIn born\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e255\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOut born\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eType of current pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingleton\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMultiple\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrimiparous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMultiparous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eGravidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrimigravida\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMultigravida\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e277\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67.40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGrand multigravida\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.73\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 \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eNeonatal baseline characteristics and service delivery factors\u003c/h2\u003e \u003cp\u003eBoth sexes were almost equally represented with a male to female ratio of 0.97 (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The median (IQR) weight of the neonates was 1600 (1400\u0026ndash;2000) grams. Minimum and maximum gestational ages at birth were 28 and 36 weeks, respectively. Almost a quarter, 24.33% of the neonates had 1st minute APGAR score of less than 7. Additionally, 41.85% and 93.43% of admitted neonates were small for gestational age (SGA) and given antibiotics respectively. As Ninety-two per cent of preterm neonates have at least one form of medical complication \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Hypothermia (43.80%) and jaundice (13.14%) were identified as the highest and lowest complications occurred respectively.\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\u003eNeonatal baseline characteristics and service delivery factors of preterm neonates admitted from January 2021-December 2022 to NICU of BHUTH and YGH, 2023(n\u0026thinsp;=\u0026thinsp;411).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercent (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex of the neonate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e208\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBirth weight (BW)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2.5kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e227\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1.5kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eGestational age (GA) in weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 to \u0026lt;\u0026thinsp;37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e185\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e45.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 to \u0026lt;\u0026thinsp;34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 to \u0026lt;\u0026thinsp;32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1st minite APGAR score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e5th minute APGAR score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e323\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eWeight for gestational age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSmall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAppropriate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e239\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eKangaroo mother care\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e196\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAntibiotic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e384\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eContinuous Positive Airway Pressure (CPAP)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e374\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLocation of NICU neonates admitted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYGH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e199\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBHUTH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFrequency of order revision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;24 hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e318\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e77.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;24 hours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.63\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 \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eTime to initiate TF and overall survival function of preterm neonates\u003c/h2\u003e \u003cp\u003eThe overall incidence rate of TF was calculated using person-days of follow up as a denominator for the entire cohort. Accordingly, a total of 411 premature neonates were followed for a total of 690 neonate-days of observation with a minimum of 1 and maximum of 6 days. During the follow up period 301 (73.2%), 78 (19%), 28 (6.8%), and 4 (1%) premature neonates started TF, died, referred and left against medical advice, respectively.\u003c/p\u003e \u003cp\u003eOur study's result indicates that the overall incidence density of TF initiation was reported as 43.6 per 100 neonate-days. Moreover, the median (IQR) time to initiate TF was found to be 2 (\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) days. Additionally, in the first day (24 hours), only 66 out of 411 neonates (16.6%) initiated TF (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). By the end of 6 days (144 hours), only 24 neonates remained, with 14 starting TF, 10 being censored, and the survival probability dropping to 0.0359 (95% CI: 0.01 to 0.074).\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\u003eThe life table analysis of preterm neonates to start TF among preterm neonates admitted from January 2021-December, 2022 to NICU of BHUTH an YGH, 2023 (n\u0026thinsp;=\u0026thinsp;411).\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\u003eTime interval\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal beginning\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStarted Trophic Feeding\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCensored\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSurvival probability\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95%CI of survival probability\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e411\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.8338\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e(0.79, 0.87)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e317\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.5326\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e(0.48, 0.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e182\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.3800\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e(0.33, 0.43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u0026ndash;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.2272\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e(0.18, 0.27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.1363\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e(0.09, 0.18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.0359\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e(0.01, 0.074)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eComparison of survivorship functions among different categorical variables.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eKaplan-Meier curves (KMc) constructed to compare the overall survival patterns over time for between different groups. Similarly, log-rank test used in conjunction with KM curves to assess if the observed differences in survival between groups were statistically significant. Preterm neonates born to mothers with APH exhibited a significantly later onset of TF compared to those born to mothers without APH \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e Likewise, the median time to TF commencement was statistically significant (log-rank test\u0026thinsp;=\u0026thinsp;12.79, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Neonates with sepsis experienced a significantly delayed TF initiation compared to those without sepsis \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e In a similar vein, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows that a median time of 2 days for preterm neonates and 3 days for those with sepsis was significantly different (Log-rank test\u0026thinsp;=\u0026thinsp;21.87, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMedian survival time and log rank test of equality of survivorship to start TF among preterm neonates admitted from January 2021-December 2022 to NICU of BHUTH and YGH, 2023 (n\u0026thinsp;=\u0026thinsp;411).\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\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMedian survival time in days (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLog rank test χ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePROM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e6.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.0103\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAPH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e12.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.0003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMode of delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSVD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e17.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMaternal HIV/AIDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2, )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e8.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.0036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBirth weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e5.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.0192\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGestational age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e7.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.0052\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eKangaroo mother care\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e17.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHypothermia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e11.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.0008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSepsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e21.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLevel of health care NICU located\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003csup\u003e0\u003c/sup\u003e (YGH)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.5, 2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003csup\u003e0\u003c/sup\u003e (BHUTRH)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2.68, 3.31)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003eKey: 2\u003c/b\u003e\u003csup\u003e\u003cb\u003eo\u003c/b\u003e\u003c/sup\u003e: \u003cb\u003eSecondary; 3\u003c/b\u003e\u003csup\u003e\u003cb\u003eo\u003c/b\u003e\u003c/sup\u003e: \u003cb\u003eTertiary\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePredictors of time to initiate trophic feeding among preterm neonates\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn order to analyze the association between independent variables and time to initiate TF, first bi-variable cox regression was performed. Those variables with p-value of \u0026lt;\u0026thinsp;0.25 in bi-variable cox regression were entered in to multivariable cox regression for adjusting the potential confounding variables. Accordingly, in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, the identified significant predictors influencing the time to initiation of TF among preterm neonates at p-value of \u0026lt;\u0026thinsp;0.05 are displayed.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable cox-proportional hazard regression on predictors of time to initiate TF among preterm neonates admitted from January 2021-December, 2022 to NICU of BHUTH and YGH, 2023 (n\u0026thinsp;=\u0026thinsp;411).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003ePredictor variables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eTrophic Feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCHR(95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAHR(95% CI)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStarted\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCensored\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePROM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.34 (1.003,1.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.16 (0.85,1.57)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMode of delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOperative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSVD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.43(1.12, 1.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.64 (1.26, 2.13)***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePreeclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.34 (1.005, 1.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.27 (0.94, 1.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAPH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e282\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.93 (1.21, 3.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.63 (0.98, 2.71)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eGestational age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 to \u0026lt;\u0026thinsp;37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e148\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 to \u0026lt;\u0026thinsp;34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.71 (0.54,0.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.61 (0.46,0.81)**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 to \u0026lt;\u0026thinsp;32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.77 (0.58, 1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.92 (0.67,1.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBirth weight (gram)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.77 (0.59, 1.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.45 (0.34, 0.60)***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eKMC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.69(0.54, 0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.59 (0.46, 0.79)***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMaternal HIV/AIDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e281\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.64 (1.04,2.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.50 (0.94,2.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNeonatal sepsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e208\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.58 (1.23, 2.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.76 (1.36, 2.28)***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHypothermia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.37 (1.09, 1.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.51 (1.19, 1.93)**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e122\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLevel of hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003csup\u003e0\u003c/sup\u003e (YGH)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e137\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.76 (0.61, 0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.78 (0.62, 0.99)*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003csup\u003e0\u003c/sup\u003e (BHTH)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cb\u003eNote\u003c/b\u003e: 2\u003csup\u003e0\u003c/sup\u003e: secondary, 3\u003csup\u003e0\u003c/sup\u003e: Tertiary; *statistically significant p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05, **statistically significant p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.01, ***statistically significant p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001. CHR-crude hazard ratio, AHR-adjusted hazard ratio, SVD-Spontaneous vaginal delivery, CS- Cesarean section, APH-Antepartum hemorrhage, WFGA-Weight for gestational age, KMC-Kangaroo mother care, CI-confidence interval.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNotably, neonates born vaginally were 64% more likely to initiate TF sooner compared to those born by cesarean section (AHR: 1.64, 95% CI: 1.26, 2.13). Preterm neonates between 32 and 34 weeks gestation had a delayed initiation of TF compared to their more mature counterparts (\u0026ge;\u0026thinsp;34 weeks) (AHR: 0.61, CI: 0.46, 0.81). Additionally, absence of kangaroo mother care was associated with a 41% reduced likelihood of earlier TF initiation (AHR: 0.59, CI: 0.46, 0.79). Likewise, a very LBW (\u0026lt;\u0026thinsp;1500gm) preterm neonates had a 55% reduced chance of starting TF on time compared to those with (\u0026gt;\u0026thinsp;1500g) (AHR\u0026thinsp;=\u0026thinsp;0.45 (0.34, 0.60). Interestingly, the absence of sepsis was also a significant predictor, with neonates without sepsis being 76% more likely to initiate TF compared to those with infection (AHR: 1.76, CI: 1.36, 2.28). Furthermore, the absence of hypothermia was associated with a 51% increased likelihood of earlier TF initiation (AHR: 1.51, CI: 1.19, 1.93). Finally, the level of hospital (YGH-level 2) was associated with a slight delay in initiating TF (AHR: 0.78, CI: 0.62, 0.99).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study's objectives were to ascertain when TF was started and its determinants in preterm newborns hospitalized to Yabello General Hospital and Bule Hora University Teaching Hospital's NICU between January 1, 2022, and September 30, 2022. As a result, of the 411 neonates observed on the first day of follow-up, 21.93% began TF, and 28 were censored. However, only 24 were left at the end of the five-day follow-up, with 14 of them having started TF. The overall incidence density in our sample was 43.6 per 100 neonate days. This means, out of every 100 days that newborn babies were observed in our study, TF was started in an average of 43.6 of those days. The median (IQR) time to TF onset of was 2 (\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) days. Moreover, he study revealed a significant increase in preterm neonatal mortality in Ethiopia, with 113.04 deaths per 1000 neonate-days, a significant increase from previous research. GA (\u0026gt;\u0026thinsp;34 weeks), SVD, the absence of sepsis, and the absence of hypothermia increase the probability of early initiation of TF by 64%, 76%, and 51%, respectively. Conversely, it was discovered that delayed TF start was caused by BW (\u0026lt;\u0026thinsp;1500 kg), lack of kangaroo mother care, and being admitted to a level-2 hospital.\u003c/p\u003e \u003cp\u003eIn our study, we found that only 21.93% of preterm neonates initiated feeding within the first 24 hours of birth, indicating that many did not start within this optimal timeframe. The study's findings are lower than previous studies in Portugal 44% (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e), Tuscany Italy (74.1%) (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e), Iran (36%) (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e), Nigeria and Kenya 48% (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e), New Zealand (60%) (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), Addis Ababa (29.9%) (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) and Amhara, Northwest Ethiopia (24.76%) (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The discrepancy may be due to differences in service quality, and availability of specialized facilities, milk banks, study period length, sample size, and design between the studies. Moreover, nearly half, (46.74%) of preterm neonates initiated TF feeding within 48 hours of birth. This is comparable with a study conducted in Addis Ababa, Ethiopia (48.2%) (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). However, it is lower than the findings from Nigerian Special Care Baby Unit (66.7%) (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e), Iran (63.2%) (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e), Uganda rural hospitals (80%) (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) and New Zealand (80%) (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). This highlights a significant delay in initiating TF among preterm neonates and creates concerns about high neonatal mortality as evidenced by our study where, over 50% of the neonate died within the first 48 hours of life. This could be because of their initial treacherous condition. The result of this study regarding incidence density of TF is lower than the result of a follow up study conducted in northern Ethiopia (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), where the incidence density of starting TF was 48 per 100 neonate-days. Moreover, the median (IQR) time of starting TF found in our study 2 (IQR: 1\u0026ndash;4) days is slightly higher than the result of a follow up study conducted in China (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e) and a retrospective study in New Zealand (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) which had a similar median time of 1 day. This discrepancy might be due to difference in service delivery quality, hospital level, having well-equipped institution, sample size and study settings. However, consistent with a longitudinal study in Ethiopia in which median time to start TF was less than 2 days (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) and a multicenter observational follow up study in Nigeria and Kenya (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e), which might be due to similarity in study design and characteristics of study subjects. This implies that the presence of a significant delay to initiate TF for studied preterm neonates.\u003c/p\u003e \u003cp\u003ePreterm neonatal mortality (NMR) was found to be surprisingly common in our study. We found an astounding 113.04 deaths per 1000 neonate-days, a significant increase above earlier research done in various parts of Ethiopia. From 27 per 1000 neonate-days in southern Ethiopia (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e), 29.438 per 1000 neonate-days in Addis Ababa, Central Ethiopia (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e) and to 75.63 per 1000 neonate-days in northwestern Ethiopia (\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e), these previous investigations revealed substantially lower fatality rates. The NMR of 45.15 per 1000 neonate-days was reported in a study conducted in Hawassa City, Ethiopia (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), which is geographically similar to our study area. This is noteworthy. Even the neighboring African country, Burkina Faso had a much lower rate, 1.93 deaths per 1000 person-days (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e). The study's unexpected high NMR result led to a potential explanation of a low proportion of neonates initiating TF early in their lives. Previous research suggests that preterm neonates who don't receive TF early are more susceptible to death (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e). Studies have shown that early TF initiation offers several benefits \u0026ndash; it reduces the length of hospital stays, lowers infection rates, and promotes gut development (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Conversely, a delay in starting TF might hinder the maturation of the gut, leading to a weakened immune system (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e). This, in turn, could significantly increase the risk of complications like Necrotizing Enterocolitis (NEC) and various infections, ultimately contributing to higher neonatal mortality (\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e). Therefore, we strongly suggest that, in particular, for susceptible groups such as preterm newborns, targeted interventions encouraging early TF initiation could drastically lower NMR rates and increase survival rates.\u003c/p\u003e \u003cp\u003eIn this study, the chance of starting TF on time was 55% reduced among a very low birth weight (\u0026lt;\u0026thinsp;1500gm) preterm neonates when compared to those with a birth weight of \u0026gt;\u0026thinsp;1500gm. This finding is in line with the results of retrospective longitudinal a study in China (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e), a retrospective study in New Zealand (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) and a multicenter prospective study conducted in Ethiopia (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). This might be due to perceived under-development of organs and low readiness to enteral feeding of preterm neonates with lower birth weight. However in contrast to this, guidelines on feeding of very low birth weight infants recommend early initiation of TF within 1 day after birth, also for this group of preterm neonates (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). This result highlights the importance of individualized care plans based on birth weight in order to insure early TF for VLBW preterm neonates.\u003c/p\u003e \u003cp\u003eAmong preterm neonates with a gestational age of less than 34 weeks, there was a statistically significant 39% reduction in the likelihood of initiating TF in comparison to neonates with a gestational age of 34 weeks or more. This result is consistent with findings of observational prospective follow up study in Italy (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e), retrospective follow up study in China (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e), a cross sectional study carried out in two of African countries (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e), a multicenter prospective study conducted in Ethiopia (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), prospective follow up study conducted in northern Ethiopia (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) and cross sectional study in Spain (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), which revealed delayed commencement of TF among newborns with lower gestational age. This might be due to lack of intestinal maturation, anxiety of feeding resistance, and perceived danger of NEC, preterm neonates born before 34 weeks of pregnancy may have gastrointestinal issues. This implies that early identification and support of lower gestational age preterm neonates may improve the time to initiate TF among this group of preterm neonates.\u003c/p\u003e \u003cp\u003eThe study found that preterm neonates delivered through spontaneous vaginal delivery had a 64% higher likelihood of starting TF compared to those delivered through CS, possibly due to delayed breast milk provision. The study's findings align with a multicenter prospective follow-up conducted in northern Ethiopia (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), prospective follow-up conducted in Addis Ababa, Ethiopia (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e), and Italy(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). This might be because of the reason that newborn's post-delivery needs may require additional monitoring and assistance, while the mother's recovery from the surgery may take longer. The result implies that preterm neonates delivered with CS are at risk of experiencing delayed initiation of TF and related complications. Thus, the healthcare providers must closely monitor both mothers and babies post-delivery and initiate enteral feeding as soon as the baby is stable and ready. However, this finding is in contrast with a result of observational retrospective follow up study conducted in China which revealed lack of significant association of delivery mode and time to initiate enteral feeding (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). This discrepancy might be due to difference in characteristics of studied subjects, sample size and study setup.\u003c/p\u003e \u003cp\u003eWHO recommended KMC for preterm or low-birth-weight infants, starting in healthcare facilities or at home, and lasting 8\u0026ndash;24 hours daily (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e). In line with this evidence, in our study, absence of KMC was associated with a 41% reduced likelihood of earlier TF initiation as compared to those with the care. Similar to this finding, a retrospective follow up study in Turkiye has identified KMC as a main factor to improve enteral feeding skills among preterm neonates (\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e). Moreover, a prospective cohort study done in a teaching hospital in India identified that early KMC was safe and associated with reduced time to full feeds (TFF) in preterm neonates (\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e). A meta-analysis of randomized controlled trial studies reported that KMC encourages early breastfeeding initiation among preterm and low birth weight infants (\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e). This implies that KMC is a gentle, effective method for preterm infants, promoting their health and well-being by allowing early discharge and avoiding agitation in busy wards (\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e). On the other hand, preterm neonates without hypothermia had a 51% higher hazard of starting TF when compared to those with hypothermia. This is line with a study conducted in Kuala Lumpur Maternity Hospital (\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e). This might be due to the fact that most preterm neonates with hypothermia often receive radiant warmer treatment and stay separated from mothers, making early enteral feeding unsuitable. This implies the significance of effective temperature regulation and thermal management strategies in the care of preterm neonates to facilitate timely initiation of TF.\u003c/p\u003e \u003cp\u003eIn this study, the hazard of starting TF was 76% increased among premature neonates without sepsis as compared to those with sepsis. This finding is supported with a result of a retrospective study conducted in Kaplan medical center, Israel (\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e), Addis Ababa, Ethiopia (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e), and Maharashtra, India (\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e). This similarity might be due to the fact that sepsis can cause decreased gut motility, increased risk of NEC (\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e), and damage the gut lining (\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e), making it difficult for neonates to tolerate enteral feeding. Thus, the healthcare providers may delay TF initiation to control infection, reduce NEC risk, and minimize gut permeability. However in contrast to this, guideline on TF does not consider sepsis as contraindication of TF among premature infants and recommends enteral feeding to be initiated early for this group of preterm infants (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The result implies early prevention and treatment of sepsis among preterm neonates might support timely initiation of TF.\u003c/p\u003e \u003cp\u003eOur study revealed inconsistency in how TF is initiated for preterm neonates across different healthcare levels. We observed a surprising trend \u0026ndash; neonates admitted to the secondary-level hospital (YGH) were 22% less likely to receive TF compared to those in the tertiary hospital (BHTRH). This finding is particularly concerning, as timely initiation of TF is crucial for the survival and development of preterm infants. Similar trends were recognized in prior research conducted in Addis Ababa, Ethiopia (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e), highlighting a potential issue within the Ethiopian healthcare system. Additionally, studies across geographically distinct locations like Nigeria and Kenya have reported similar disparities (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). This observed similarities suggests a concerning possibility that preterm neonates in less-resourced facilities may face systemic disadvantages when it comes to accessing essential and life-saving interventions like TF. Moreover, the secondary hospitals might have lack of resources, trained personnel, and logistical challenges. Therefore, our study highlights the need for a comprehensive investigation into the disparity in access to TF across healthcare levels, including capacity building, resource allocation, and logistical processes.\u003c/p\u003e \u003cp\u003eTo the best of our knowledge our study is among few in Ethiopia conducted to determine the time to initiate trophic feeding, involving advanced statistical analysis. However, due to retrospective nature, incomplete data was excluded, potentially introducing selection bias. The data was collected from secondary sources, potentially missing important predictors like nurse-patient ratio and breast milk availability.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study highlights significant opportunities to improve early trophic feeding (TF) practices for preterm neonates. Only 16.6% initiated TF within the first 24 hours, suggesting a gap between current practice and optimal timing. Additionally, disparities exist across healthcare levels, with neonates in secondary-level hospitals 22% less likely to receive TF compared to those in tertiary centers. Factors promoting early TF initiation include: Vaginal delivery (SVD), Absence of sepsis or hypothermia and Kangaroo mother care. Conversely, early TF initiation is hindered by: Lower gestational age (32\u0026ndash;34 weeks), Lower birth weight (\u0026lt;\u0026thinsp;1500g), Lack of kangaroo mother care and Admission to a secondary hospital. Based on these findings, we propose the following feasible and practical recommendations: Implement clear guidelines for initiating TF based on gestational age, birth weight, and clinical condition, ensuring consistency across healthcare levels. Provide training and resources to healthcare professionals at secondary facilities to ensure they feel confident initiating TF for eligible preterm neonates. Encourage and support kangaroo mother care practices for all eligible preterm neonates, recognizing its positive impact on TF initiation. Ensure adequate staffing and equipment\u0026rsquo;s are available at both secondary and tertiary hospitals to support early TF implementation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical clearance was obtained from the Institutional Research Ethics Review Committee (IERC) of Institute of Health (IOH), Bule Hora University, ensuring the study adheres to ethical research principles.\u0026nbsp;The study involved the secondary analysis of data from preterm neonates and their mother\u0026rsquo;s medical records at\u0026nbsp;Bule Hora University Teaching Hospital (BHUTH) and Yabello General Hospital (YGH)\u0026nbsp;specifically from the NICU. Following IERC approval, submissions were made to the administrative offices of both BHUTH and YGH for their respective approvals. \u0026nbsp;Since the study was a retrospective study, informed consent would not seek from individual participants. However, we obtained written permissionfrom the heads of the NICU at each hospital\u0026nbsp;to access the medical records for research purposes.\u0026nbsp;This has been approved by the IOH-\u0026nbsp;IRERC.\u0026nbsp;Data were anonymized, stored securely, and only accessible to the principal investigators to maintain participant confidentiality and minimize identification risks.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor those who are interested; the datasets of this study could be accessed from the corresponding author on reasonable request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declared no potential competing of interest with respect to the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBule Hora University has supported the study financially. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAF, TY: Conceptualization, Methodology, Data analysis, Writing - Original Draft, Writing - Review \u0026amp; Editing,\u0026nbsp;interpretation of data and approved the final manuscript. AE, MG: Data collection, Investigation, Writing - Review \u0026amp; Editing,\u0026nbsp;interpretation of data and approved the final manuscript. DH, MS: Supervision, Project administration, Writing - Review \u0026amp; Editing, interpretation\u0026nbsp;of data and approved the final manuscript.\u0026nbsp;All authors have made substantial contributions to this manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe acknowledge the financial support provided by Bule Hora University, Research Ethics, Dissemination and Publication Directorate, which significantly facilitated to conduct our study. Our sincere gratitude extends to the chief administrators of Bule Hora University Teaching Hospital and Yabello General Hospital, as well as the respective NICU department heads, for their invaluable assistance and unwavering support in facilitating data extraction process. Finally, we commend the dedication and professionalism of our data extraction team and supervisors, whose meticulous work ensured the quality and integrity of the extracted data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Health Organization (WHO). Preterm birth: 2021. https://www.who.int/news-room/fact-sheets/detail/preterm-birth.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization (WHO). Preterm birth 10 May 2023 [cited 2024 April 14]. Available from: https://www.who.int/news-room/fact-sheets/detail/preterm-birth.\u003c/li\u003e\n\u003cli\u003eCao G, Liu J, Liu M. Global, Regional, and National Incidence and Mortality of Neonatal Preterm Birth, 1990-2019. JAMA pediatrics. 2022;176(8):787-96.\u003c/li\u003e\n\u003cli\u003eSendeku FW, Beyene FY, Tesfu AA, Bante SA, Azeze GG. Preterm birth and its associated factors in Ethiopia: a systematic review and meta-analysis. 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The Nutrient Intakes And Feeding Prescriptions Of Low Birth Weight Infants At Chris Hani Baragwanath Academic Hospital. 2017.\u003c/li\u003e\n\u003cli\u003eNakubulwa C, Musiime V, Namiiro FB, Tumwine JK, Hongella C, Nyonyintono J, et al. Delayed initiation of enteral feeds is associated with postnatal growth failure among preterm infants managed at a rural hospital in Uganda. BMC pediatrics. 2020;20(1):86.\u003c/li\u003e\n\u003cli\u003eGidi NW, Goldenberg RL, Nigussie AK, McClure E, Mekasha A, Worku B, et al. Incidence and associated factors of extrauterine growth restriction (EUGR) in preterm infants, a cross-sectional study in selected NICUs in Ethiopia. BMJ paediatrics open. 2020;4(1):e000765.\u003c/li\u003e\n\u003cli\u003eTerefe A, Demtse A, Abebe F, Mislu E, Tachbele E. Predictors of time to full enteral feeding in low birth weight neonates admitted to neonatal intensive care unit: a prospective follow up study. BMC pediatrics. 2024;24(1):64.\u003c/li\u003e\n\u003cli\u003eMalhotra Y, Nzegwu N, Harrington J, Ehrenkranz RA, Hafler JP. Identifying Barriers to Initiating Minimal Enteral Feedings in Very Low-Birth-Weight Infants: A Mixed Methods Approach. American journal of perinatology. 2016;33(1):47-56.\u003c/li\u003e\n\u003cli\u003eDe Waard M, Li Y, Zhu Y, Ayede AI, Berrington J, Bloomfield FH, et al. Time to Full Enteral Feeding for Very Low-Birth-Weight Infants Varies Markedly Among Hospitals Worldwide But May Not Be Associated With Incidence of Necrotizing Enterocolitis: The NEOMUNE-NeoNutriNet Cohort Study. 2019;43(5):658-67.\u003c/li\u003e\n\u003cli\u003eImamn OZ, Nabwera MH, Tongo OO, Pauline EA, Andang\u0026rsquo;o, Abdulkadir I, et al. Time to full enteral feeds in hospitalised preterm and very low birth weight infants in Nigeria and Kenya. PloS one. March 8, 2024;19(3):1-16.\u003c/li\u003e\n\u003cli\u003eHealth Management Information System (HMIS) team, Head H. Bule Hora University Teaching Hospital. 2023.\u003c/li\u003e\n\u003cli\u003eHealth Management Information System (HMIS) team, head H. Yabello General Hospital. 2023.\u003c/li\u003e\n\u003cli\u003eElisa Civardi, Francesca Garofoli, Chryssoula Tzialla, Margherita Pozzi, Stronati M. Trophic feeding for very preterm or very low birth weight infants. Italian Journal of Pediatrics. 2015.\u003c/li\u003e\n\u003cli\u003eDilli D, Soylu H, Tekin N. Neonatal hemodynamics and management of hypotension in newborns. Turk pediatri arsivi. 2018;53(Suppl 1):S65-s75.\u003c/li\u003e\n\u003cli\u003eVasconcelos S, Granado C, Ribeiro MN, Vieira MJ, Vieira2 J. Enteral feeding in preterm newborns\u0026ndash; determinants of progression. J of Pediatr and Neonat Individualized Med. 2022;11(1).\u003c/li\u003e\n\u003cli\u003eBerti E, Puglia M, Perugi S, Gagliardi L, Bosi C, Ingargiola A, et al. 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Nutrition. 2023;107:111912.\u003c/li\u003e\n\u003cli\u003eOrsido TT, Asseffa NA, Berheto TM. Predictors of Neonatal mortality in Neonatal intensive care unit at referral Hospital in Southern Ethiopia: a retrospective cohort study. 2019;19(1):83.\u003c/li\u003e\n\u003cli\u003eMislu E, Arage MW, Kumsa H, Terefe A. Mortality Among Low Birth Weight Neonates on Parenteral Feeding: A Prospective Follow-Up Study. Research and Reports in Neonatology. 2024:67-84.\u003c/li\u003e\n\u003cli\u003eWondie WT, Zeleke KA, Wubneh CA. Incidence and predictors of mortality among low birth weight neonates in the first week of life admitted to the neonatal intensive care unit in Northwestern Ethiopia comprehensive specialized hospitals, 2022. Multi-center institution-based retrospective follow-up study. BMC pediatrics. 2023;23(1):489.\u003c/li\u003e\n\u003cli\u003eCoulibaly A, Baguiya A, Millogo T, Meda IB, Koueta F, Kouanda S. 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Archives of disease in childhood Fetal and neonatal edition. 2005;90(2):F147-51.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization (WHO). WHO recommendations for care of the preterm or low-birth-weight infant. Geneva: World Health Organization; 2022.\u003c/li\u003e\n\u003cli\u003eErİ l., G\u0026uuml;nlemez A. Transition Time to Full Oral Feeding Skill and its Determinants in Very Preterm Infants: A Single Center Experience. Journal of pediatric gastroenterology and nutrition. 2021;2(8).\u003c/li\u003e\n\u003cli\u003ePandya D, Kartikeswar GAP, Patwardhan G, Kadam S, Pandit A, Patole S. Effect of early kangaroo mother care on time to full feeds in preterm infants - A prospective cohort study. Early Human Development. 2021;154:105312.\u003c/li\u003e\n\u003cli\u003eMekonnen AG, Yehualashet SS, Bayleyegn AD. The effects of kangaroo mother care on the time to breastfeeding initiation among preterm and LBW infants: a meta-analysis of published studies. International breastfeeding journal. 2019;14:1-6.\u003c/li\u003e\n\u003cli\u003eHealth WHOR. Kangaroo mother care: a practical guide: World Health Organization; 2003.\u003c/li\u003e\n\u003cli\u003eBoo N, Soon C, Lye M. Risk factors associated with feed intolerance in very low birthweight infants following initiation of enteral feeds during the first 72 hours of life. Journal of Tropical Pediatrics. 2000;46(5):272-7.\u003c/li\u003e\n\u003cli\u003eFlidel-Rimon O, Friedman S, Lev E, Juster-Reicher A, Amitay M, Shinwell ES. Early enteral feeding and nosocomial sepsis in very low birthweight infants. Archives of disease in childhood Fetal and neonatal edition. 2004;89(4):F289-92.\u003c/li\u003e\n\u003cli\u003esPatwardhan G, Soni A, Rachwani N, Kadam S, Patole S, Pandit A. Factors associated with time to full feeds in preterm very low birth weight infants. Journal of tropical pediatrics. 2018;64(6):495-500.\u003c/li\u003e\n\u003cli\u003eWang Z-L, An Y, He Y, Hu X-Y, Guo L, Li Q-Y, et al. Risk factors of necrotizing enterocolitis in neonates with sepsis: A retrospective case-control study. International Journal of Immunopathology and Pharmacology. 2020;34:2058738420963818.\u003c/li\u003e\n\u003cli\u003eCotten CM. Modifiable risk factors in necrotizing enterocolitis. Clinics in Perinatology. 2019;46(1):129-43.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Preterm neonates, Trophic feeding, Predictors, Time to initiate, Survival analysis","lastPublishedDoi":"10.21203/rs.3.rs-4566019/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4566019/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe timely initiation of trophic feeding (TF) is crucial for premature newborns, but challenging due to immaturity, respiratory instability, abdominal distension, resource scarcity, and healthcare worker expertise. Moreover, there is a dearth of information on predictors of full trophic feeding time. Therefore, this retrospective cohort study aimed to investigate the time it takes and its predictors to initiate minimal enteral feeding in preterm neonates in Southern Oromia.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eA facility-based retrospective follow up study was conducted among 434 randomly selected preterm neonates admitted to NICU of Bule Hora University Teaching Hospital and Yabello General Hospital from January 1, 2021-December 30, 2022. Data were extracted by a pretested structured checklist, entered into Epidata 3.1 and then transferred to Stata version 17 for analysis. Kaplan Meier survival curve and log rank test were used to estimate survival time and a statistical comparison respectively. Bivariable and multivariable cox proportional hazard model was fitted to identify predictors of time to initiate TF and their outputs are presented using Adjusted Hazard Ratio (AHR) with 95% Confidence Intervals (CIs).\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e \u003cp\u003eIn our study, the overall incidence density rate (IDR) of initiation of TF was 43.6 per 100 neonates-days of follow-up with a median time to start TF of 2 days and also only 21.93% of newborns started TF on the first day of observation. Furthermore, Neonates born vaginally (AHR: 1.64, 95% CI: 1.26, 2.13), GA of 32\u0026thinsp;\u0026lt;\u0026thinsp;34 weeks (AHR: 0.61, CI: 0.46, 0.81), VLBW (AHR\u0026thinsp;=\u0026thinsp;0.45, CI: (0.34, 0.60), absence of KMC (AHR: 0.59, CI: 0.46, 0.79), absence of sepsis (AHR: 1.76, CI: 1.36, 2.28), absence of hypothermia (AHR: 1.51, CI: 1.19, 1.93) and secondary level of hospital (AHR: 0.78, CI: 0.62, 0.99) were associated with initiation of TF.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eWe observed a significant low rate of TF initiation and higher death rate of preterm newborn in our study as compared to the global. Preterm neonates with lower GA, no KMC, and a VLBW are more likely to have a delayed initiation. Our results highlight that, staff training on identifying neonates suitable for TF, and ensuring adequate resources for KMC in all NICU levels should be considered. Moreover, further studies are required to validate these findings and determine the influence on clinical outcomes.\u003c/p\u003e","manuscriptTitle":"How long does it take to start minimal enteral feeding in preterm Neonates admitted to NICUs in Southern Oromia, Ethiopia?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-22 21:12:36","doi":"10.21203/rs.3.rs-4566019/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2024-09-15T18:47:52+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-06-29T13:33:32+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-29T13:27:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-14T20:56:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"Italian Journal of Pediatrics","date":"2024-06-14T16:04:01+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"95a4aa56-cc98-4577-b4b2-be401db7bad3","owner":[],"postedDate":"July 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-10T16:06:30+00:00","versionOfRecord":{"articleIdentity":"rs-4566019","link":"https://doi.org/10.1186/s13052-025-01876-1","journal":{"identity":"italian-journal-of-pediatrics","isVorOnly":false,"title":"Italian Journal of Pediatrics"},"publishedOn":"2025-02-07 15:58:26","publishedOnDateReadable":"February 7th, 2025"},"versionCreatedAt":"2024-07-22 21:12:36","video":"","vorDoi":"10.1186/s13052-025-01876-1","vorDoiUrl":"https://doi.org/10.1186/s13052-025-01876-1","workflowStages":[]},"version":"v1","identity":"rs-4566019","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4566019","identity":"rs-4566019","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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