Burden and Outcomes of Respiratory Diseases in Hospitalized Neonates at a Tertiary Care Hospital in Lahore: A Cross-Sectional Study

Background: Respiratory diseases constitute a significant contributor to health issues in neonates, leading to admissions to neonatal intensive care units (NICU), and many of these neonates never recover, resulting in high neonatal mortality rates with respiratory diseases. Objective: To assess the burden of respiratory diseases in hospitalized neonates and determine their outcomes, including discharges and deaths, among those admitted to neonatal intensive care units in a tertiary care hospital in Lahore. Methods: An observational analytical cross-sectional study was conducted on 187 neonates admitted to a neonatology department of the tertiary care hospital in Lahore. Demographical data was collected by using a structured questionnaire. The analyses were conducted using R software. The chi-square test was employed to ascertain the associations between significant factors of respiratory diseases in neonates. Results: Among the respiratory conditions requiring admission, pneumonia (n=92, 49.1%) stood out as the most frequently diagnosed respiratory disease in neonates, followed by respiratory distress syndrome (RDS) (n=53, 28.3%), transient tachypnea of the newborn (TTN) (n=18, 9.62%), and meconium aspiration syndrome (MAS) (n=24, 12.8%). In terms of mortality among these respiratory conditions, pneumonia had the highest frequency (40.5%), followed by RDS (39.2%), MAS (20.2%), in neonates. Conclusion: Respiratory disorders proved to be a prevalent reason for neonatal admissions to the NICU, showcasing a significant association with neonatal mortality, especially in pneumonia, respiratory distress syndrome


Introduction
R espiratory diseases significantly contribute to mor- bidity and mortality among neonates, necessitating frequent admission to the neonatal intensive care unit 1 (NICU).The mortality rate is 2-4 times higher in neonates with respiratory disorders than in neonates unaffec-contributing significantly to respiratory morbidity.
Neonatal respiratory diseases contribute to the global disease burden and challenge healthcare in low-income countries (LIC), low-middle-income countries (LMIC) and high-income countries (HIC).In the LICs and the LMICs, neonatal respiratory distress's primary causes include preterm delivery, low Apgar scores at the first and fifth minute, meconium aspiration syndrome, pneumonia, maternal gestational diabetes, premature rupture of membranes (PROM) leading to chorioamnionitis and septicemia, caesarean delivery and transient tachypnea

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of the newborn (TTN).However, in HICs, intrapartum hypoxia, meconium aspiration syndrome and pneumonia, maternal medical diseases such as gestational diabetes mellitus, hypertension, and asthma lead to 8 neonatal respiratory distress.Furthermore, respiratory distress morbidity appears higher in countries with 9 limited resources compared to high-income settings.
A variety of pathological conditions contribute to respiratory diseases including pneumonia (22.5%), respiratory distress syndrome (RDS) (20.8%), meconium aspiration syndrome (MAS) (16.7%), sepsis (12.5%), transient tachypnea of the newborn (TTN) (11.7%), birth asphyxia (BA) (7.5%), congenital heart disease (CHD) (4.3%), and other factors.The most significant cause of neonatal respiratory diseases remains premature birth, particularly among neonates born earlier than 34 weeks gestation, leading to respiratory distress syndrome.Understanding the frequency of different causes of neonatal respiratory diseases among NICU admissions facilitates planning the management specific to the geographical location.Consequently, health professionals can devise health policies and hospital protocols using the data respiratory disease burden are employed.However, despite all these measures and efforts, respiratory diseases remain the primary cause of morbidity and mortality 14 among neonates in Pakistan.Unfortunately, there is a gap in the knowledge about the burden and outcomes of respiratory diseases in neonates, particularly in the LICs and LMICs.Therefore, the current study aims to assess the disease burden and the neonatal outcomes of respiratory diseases among neonates admitted to the neonatal intensive care unit at a tertiary care hospital in Lahore, Pakistan.

Methods
The current study was an observational analytical crosssectional study conducted on neonates admitted to the NICU of the Avicenna Hospital, Lahore.The study period was from 1 January 2022 to 31 December 2022.Geographically, Lahore is the capital city of Punjab Province, situated at 31•32′59′ ′ latitude and 74•20′37′ ′ longitude and is the second-most populous city in Pakistan and Avicenna Hospital is located at the southern urban-rural border of the city, a tertiary care hospital affiliated with the Avicenna Medical College, Lahore, Pakistan.
The study participants' geographical locations were identified and marked on Google Maps.Subsequently, a dot map was generated utilising the QGIS software version 3.2.The study protocol adhered to the guidelines outlined in the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.

Figure 1: Study map area of enrolled study participant's location in Lahore District
Our research team calculated the sample size by using winPepi software with a 95% confidence level, 5% margin of error and an expected percentage of 14.1% of TTN, the least among all respiratory diseases in neonates.The calculated sample size was 187 cases, and we used a consecutive sampling technique.The inclusion criteria were neonates with respiratory disease (RDS, MAS, TTN and pneumonia), patients within the age range of birth to 28 days, irrespective of gender, neonates with a gestational age of 28 weeks (on dating scan) and weight of more than 1000 gm.
The cases of syndromic neonates and those with congenital anomalies were excluded from the study.A structured questionnaire was used to collect data, including demographic information such as name, age, sex, and date of admission.When admission to the NICU, the chest examination was done, and the findings were recorded.As a work-up of respiratory diseases, the following tests were conducted: oxygen saturation via pulse oximetry, chest X-ray, arterial blood gases, complete blood picture (CBC), and blood culture.
The data sets were inputted into the EpiData software (version 3.1, accessible at http://www.epidata.dk/)and subjected to error and inconsistency validation through random comparisons between the digital and hard copy records.Subsequently, the data was exported to Microsoft Excel for further processing.The 'epiR and epiDisplay' packages from the R software (version 4.2.1, R Foundation for Statistical Computing, Vienna, Austria) were used for all statistical analyses.Variables with a categorical nature were measured in terms of frequencies and percentages.The Chi-square test was utilized to ascertain the association of the significant contributing factors of respiratory diseases in neonates.

Results
The neonates ranged in age from 1 to 28 days, with a mean of 15.01±7.99days.The gestational age of the subjects varied between 28 weeks and 40 weeks, with a mean of 37.4±1.9weeks.One hundred and thirtyfive (72.19%) neonates were preterm, while 52 (27.8%) were full-term neonates.One hundred and twenty-four neonates (66.3%) were male, while sixty-three (33.7%) were female, resulting in a male-to-female ratio of 2:1.Neonates which were 126 (67.37%) born via cesarean section as shown in Table 1.

Distribution of respiratory diseases in terms of outcome (Death & Discharge)
There were a total of 187 participants selected for the present study.Among these, 108 were discharged on recovery, and 79 neonates died.The flow chart presents the number of cases of respiratory distress in terms of outcome i.e. discharge and death (Figure 3).A Significant association was observed among the causes of respiratory diseases in neonates.A gestational period of 28-36 weeks significantly correlated with respiratory distress.The mode of delivery, specifically Cesarean Section (p=0.03),showed a significant association with neonatal respiratory distress.Further details are in Table 2.
Chi-Square was applied.P value <0.05 was considered significant.** highly significant results.Fisher exact test applied on causes of respiratory distress due to having one cell value less than 5.

Discussion
Respiratory diseases are a significant contributor to morbidity and mortality rates and are a prevalent ailment that necessitates admission to neonatal intensive care [15][16][17] units (NICUs) for neonates worldwide.Pakistan is an LMIC with limited resources and a significant neonatal disease burden; therefore, this study assessed the burden and outcomes of respiratory diseases among neonates admitted to a tertiary care hospital in Lahore.
The present study observed a greater incidence of respiratory diseases in males (66.3%) than in females (33.7%).This finding is consistent with earlier research that reports that the growth and development of the lungs commences during the prenatal phase, and the maturation of the lungs is comparatively more advanced [17][18][19] in the female fetus.The present study revealed a higher risk of acquiring respiratory diseases among neonates delivered via cesarean section than those delivered vaginally.The earlier studies supported our findings and reported that respiratory illnesses are more common in neonates born via caesarean section.Newborns delivered through caesarean section exhibit a higher quantity of residual lung fluid and a reduced residual capacity, resulting in a decreased secretion of surfactant into the alveolar space.Conversely, during vaginal delivery, the infant's chest compression facilitates the elimination of some fetal lung fluid, and the adrenergic stimulation associated with the process of vaginal labour promotes the release of surfactant into  as well as immediate neonatal evaluation at birth in highrisk cases, along with parental counselling and preventive strategies, to decrease the alarmingly higher neonatal mortality rate in this part of the world.
However, there are certain limitations in the present study.Our study had a relatively limited sample size compared to other research efforts, limiting our findings' generalizability.Furthermore, we did not assess the long-term neonatal outcomes in cases discharged from the NICU.As a result, we recommend conducting a comprehensive future study with more extensive sample size and prolonged follow-up period to comprehensively assess the health challenges and survival rates of infants experiencing respiratory diseases.Another limitation of the present study was that we didn't consider various management options and their impact on the neonatal outcome.This consideration could have facilitated the identification of more suitable treatments for respiratory disorders in newborns in future medical practice.

Conclusion
The study highlighted that respiratory diseases were one of the cause of neonatal admission to the Neonatal Intensive Care Unit (NICU) and were associated with neonatal mortality, particularly respiratory distress syndrome, pneumonia, transient tachypnea of the newborn, and meconium aspiration syndrome.

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the common causes and outcomes.The Sustainable Development Goals (SGD) by the United Nations General Assembly and the various policies, initiatives and programmes developed by the healthcare sectors to prevent and manage neonatal 12,13 The re-January -March 2024 | Volume 30 | Issue 01 | Page 53 search was carried out following the principles outlined in the Declaration of Helsinki and received approval from the Institutional Review Board (IRB) for Biomedical Research at Avicenna Medical College & Hospital, Lahore (Letter No. IRB-43/8/23/AVC).A total of one hundred and eighty-seven patients who met the inclusion criteria were enrolled in the study.The parents or guardians of neonates provided written informed consent.

Figure 3 .
Figure 3. Flow chart showing Outcome of Neonates Admitted to NICU

Table 2 :
Association of causes of respiratory Diseases in neonates in terms of the outcomes (Death and Discharge) Approval from the Institutional Review Board (IRB) for Biomedical Research at Avicenna Medical College & Hospital, Lahore (Letter No. IRB-43/8/23/AVC).
Approval: SK: Acquisition of data, data analysis AZ: Acquisition of data, interpretation of data