An institutional-based retrospective follow-up study was conducted from January 1, 2019, to December 30, 2021. The study was conducted at three hospitals of neonatal intensive care units in North Shoa Zone Amhara Region, Ethiopia. The selected hospitals are Debre Berhan Comprehensive, Mehal Meda General, and Enate General Hospital.

All low birth weight neonates that were admitted to the neonatal intensive care unit in a public hospital in North Shoa zone Amhara Region, Ethiopia were the source population.

Moreover, all low birth weight neonates admitted to the neonatal intensive care unit in selected hospitals found in the North Shoa Administration Zone from January 1/2019 to December 30/2021 were included.

All low-birth-weight neonates with a gestational age greater than 28 weeks who were admitted to the neonatal intensive care unit (NICU) from January 1/2019 to December 30/2021 were included. However, Only incomplete chart records and records which were not available during the data collection period were excluded from this study.

The sample size was determined using a double population proportion formula by using major predictor variables (home delivery, maternal age >35, sepsis and respiratory distress syndrome) from another study conducted at Bahirdar. Maternal age was considered an independent predictor of mortality since it gives a maximum sample size; from that study proportion of those exposed to Death was 38.7% and non-exposed to Death was 24.8% (15, 16) Using the Epi info software version 7, to one allocation ratio of exposed to non-exposed (1:1) was assumed. Finally, by using a 95% level of confidence, with a power of 80%, the total sample size was 416. A simple random sampling method was used to select three hospitals from 10 governmental hospitals, and LBW neonatal cards were proportionally allocated according to their total LBW neonatal admission at the NICU.

There were 2,507 neonates with low birth weight admitted to the NICU of three hospitals from 2019 to 2021. The neonate's medical record number (MRN) was used as a sampling frame. The sample was proportionally allocated for each hospital.

Neonatal mortality: The death of the newborn from the time of birth up to 28 completed days of life.

Neonatal Respiratory Distress Syndrome: diagnosed based on the presence of one or more of the following signs: an abnormal respiratory rate, expiratory grunting, nasal flaring, chest wall recessions with or without cyanosis (17).

Event: Low birth weight neonates with the outcome of Death in the study period.

Censored: Low birth weight neonates with predictors other than Death (lost follow-up, survived over the follow-up period, referred to other health facilities against medical treatment).

Survival time: It is the time from admission to NICU with LBW to the occurrence of an event or censoring.

Survival status: Outcome of neonates, either death or censored.

Birth asphyxia: is diagnosed based on the World Health Organization (WHO) definition of “the inability to initiate and maintain breathing at birth” (18).

The data collection tool was taken from the standardized national neonatal and delivery room registration book. The checklist includes maternal and neonatal socio-demographic predictors, neonatal medical predictors, maternal medical and obstetric predictors, and the outcome of a low birth weight neonate, date of admission, and date of Death or censored. The first day of admission was used as the start of the follow-up period, while the last day of an event or censored occurrence was used as the end. All LBW neonatal medical registration numbers were obtained from the NICU ward. The required number of medical registration cards was chosen based on their eligibility criteria. The medical record office was then contacted to obtain selected medical cards. Finally, data collectors reviewed selected charts.

The data was gathered by three trained nurses who had Bachelor of Sciences in Nursing (BSCN) and were supervised by the principal investigator.

A pretest with 5% of the sample population was conducted to ensure data quality. A 1-day training was given for data collectors and supervisors before the actual data collection. The supervisor carried out close supervision throughout the data collection time. The principal investigator entered and cleaned the data.

Data were entered, cleaned, edited, and coded using Epi data version 4.2, Then exported to STATA 14 statistical software for analysis. Descriptive statistics (mean, standard deviation, median, frequency and percentages) were computed depending on the nature of the variable, and results were presented as graphs and tables. The outcome of each participant was dichotomized into censored or death. The incidence density rate (IDR) was calculated for the entire study period. Kaplan Meir plot with log-rank tests was used to compare survival curves. Before performing the Cox-proportional hazard regression, model goodness-of-fit was checked by Cox Snell residuals (Figure 1). Model fitness was tested by using Schoenfeld residuals test for proportional assumption and it was fitted with a total global test result of 0.4205.

Those variables with a p-value <0.05 were entered into the model. Multi-collinearity was also checked. For each independent predictor, Bi-variable Cox Proportional Hazard regression was performed. The variable with a p-value <0.25 in bivarable analysis was included in multivariable Cox proportional hazard regression. Adjusted hazard ratio with a 95% confidence interval and p-value <0.05 was used to measure the strength of association and identify statistical significance.

Ethical approval was obtained from the institutional review board of Asrat Woldeyes Health Science Campus (protocol number IRB-061). Informed consent was obtained from a legal guardian. This study was conducted per the Declaration of Helsinki. All methods were carried out per relevant guidelines and regulations.

During the follow-up time, 2,507 LBW neonates were admitted to selected hospitals. Out of these, 416 neonatal charts were reviewed. 324 (77.8%) were born from maternal Ages 18–35 years. The median age of mothers was 30 years, with an interquartile range of 9 years.

Among all mothers enrolled in the study, the majority of 301 (72.4%) mothers had given birth at a health institution. In addition, nearly half of the neonatal admissions occurred from 1 to 7 days of age (202, 48.56%) (Table 1).

Among 416 study participants, more than half (55.1%) of them were males. The majority of mothers, 324 (77.8%), were belonging to 18–35 years group. Among admitted neonates, 155 (37.26%) of them were in the gestational age (GA) group of very premature (28–32 weeks), of which 60 (56.07%) died, which was higher than premature (41.12%) and mature neonates (2.80%). The mean gestational age was 33.7 ± 2.5 SD weeks (95% CI: 33.53, 34.02) (Table 1).

Among 416 mothers, 272 (65.38%) of them had ANC follow-ups at nearby health institutions. From the study, the majority of mothers who had ≥ two pregnancies accounted for 194 (46.63%) and among them, 67 (62.62%) died. Of all mothers included in the study, 228 (54.8%) of mothers were diagnosed with obstetric problems. Of all births, the highest percentage of birth was given by spontaneous vaginal delivery, 277 (66.59%) (Table 2).

Among the total mothers enrolled in this study, 107 (25.72%) mothers had HIV/AIDS, and 74 (17.79%) had Anemia, 105 (25.4%) of mothers had Diabetes mellitus (DM, and nearly half, 49.53%, of their neonates died. Furthermore, 108 (25.96%) mothers had a history of hypertension, and 77 (18.51%) mothers had a History of Tuberculosis (TB) (Table 3).

The significant admission medical problems documented among neonates admitted to NICU during the follow-up period were low Apgar scores (1st and 5th minute Apgar score <7, 186 (44.71%) and, 160 (38.46%), sepsis 204 (49.04%), PNA 136 (32.69%), Jaundice 80 (19.23% and RDS 141 (33.89%). Among admitted neonates with RDS, more than half, 54 (50.47%), died, and Sepsis was the leading cause of Death which was 68 (63.55%). The median neonatal birth weight at admission was 1,600 g, with an IQR of 500 g (Table 4).

A total of 416 LBW neonates were followed for 0–28 days. The overall proportion of neonatal mortality among the LBW neonate was 107 (25.72%) (95% CI: 21.50, 29.93) (Figure 2).

The overall incidence rate of mortality was 42.83 per 1,000 person-days (95% CI: 35.34, 51.77) with 2,498 person-days observation. In this study, the incidence rate of Mortality among LBW neonates within the first 24 h, 1–7 and 7–28 days were 60, 35 and 30 per 1,000 person-days observation, respectively (Table 5).

The incidence rate of mortality among LBW neonates with 28–32 gestational age, 33–36 and ≥37 gestetional age were 60, 44 and 3 per 1,000 person-days observation respectively.

The overall Kaplan–Meier estimate showed that LBW neonates’ survival probability was high on the first day of admission, which comparatively decreases as follow-up time increases (Figure 3).

During the first day of hospital stay, a maximum (94.95%) (95% CI: 92.36, 96.68) probability of survival was observed with a standard error of 0.01. The first quartile survival time was 7 days (95% CI: 5, 8). The overall survival ship probability of LBW neonates admitted to NICU throughout follow-up time remained at 49.43% (95% CI: 38.66, 59.31%).

The overall median survival time of neonates admitted to NICU in the study was 15 days (95% CI: 14) with a standard error of 1.37. This study also shows that the probability of neonatal survival on the 7th and 14th day of hospital stay was 72.06% (95% CI: 66.35, 76.98, SE = 0.02) and 53.3.03% (95% CI: 43.5, 62.5, SE = 0.049), respectively (Figure 2).

LBW neonates diagnosed with Respiratory Distress Syndrome (RDS) in this study had a mean survival time of 14 days (95% CI: 11).

At the 28 days of hospital stay, the overall survival of neonates with RDS and without RDS was 40.79% and 55.7%, respectively. This survival time difference was statistically significant with a p-value = 0.0012.

Neonates diagnosed with Sepsis had a lower survival time than those without Sepsis, with an overall survival status of 42.63% and 58.87%, respectively, at the end of the follow-up period. P-value = 0.0026 (Figure 4).

This study also revealed that LBW neonates born from those mothers who hadn't Diabetes mellitus (DM) at baseline of admission had a longer survival time than those with DM (with a median of 7 days 95% CI: 5, 11) and (95% CI: 14) respectively. The Overall survival probability for LBW neonate mothers with DM and non-diabetic was 31.40% and 54.79%, respectively. This difference was statistically significant with a p-value = 0.000 (Figure 5).

The Cox proportional hazard model was used to identify predictors of Mortality in LBW neonates. In bivariate Cox proportional hazard regression, sex, birth weight, neonatal age, place of delivery, Antenatal care follow-up, mode of delivery, parity, Gestational Age, multiple pregnancies, preeclampsia, maternal history of DM, maternal history of HIV, maternal history of hypertension, maternal history of Anemia, birth weight, Sepsis, jaundice, RDS and NEC were significant predictors of Mortality in LBW neonates at (p-value <0.25). In a multivariate proportional hazard model, neonatal sepsis, RDS, maternal history of DM, maternal history of HIV/AIDS, Twin pregnancy, preeclampsia, and extremely low birth weight, and Very low birth weight were independent predictors of LBW neonatal mortality at (p value <0.05).

Multivariate analysis revealed that neonates born with a birth weight less than 1,000 g were 8.4 times higher hazard of Death as compared to neonates weighing between 1,500 and 2,499 g (AHR: 8.4; 95% CI: 4.38, 16.14). LBW neonates born with birth weight between 1,000 and 1,499 g were 3.5 times higher hazard of Death than as compared to neonates weighing between 1,500 and 2,500 g (AHR: 3.5; 95% CI: 1.95, 6.51).

The hazard of Death in LBW neonates with Sepsis was 1.5 times higher than compared to those neonates without Sepsis (AHR: 1.53; 95% CI: 1.01, 2.32). Low birth weight neonates with RDS were also 1.6 times more at risk of dying than those without RDS (AHR: 1.6; 95% CI: 1.15, 2.63).

LBW neonates, Mothers with DM, were 2.5 times more hazardous to die than LBW neonate mothers without DM (AHR: 2.5; 95% CI: 1.70, 3.87). Low birth weight neonates with mothers with multiple pregnancies were 1.7 (AHR: 1.7; 95% CI: 1.42, 3.29) times riskier to die than those without multiple pregnancies. LBW neonates from Mothers with preeclampsia were 1.8 times more hazardous to die than mothers without preeclampsia (AHR: 1.83; 95% CI: 1.23, 2.73).

LBW neonates from Mothers with HIV were 2.2 times more hazardous to die than mothers without HIV (AHR: 2.2; 95% CI: 154, 3.42) (Table 6).