The neonatal period is one of the most vulnerable stages of life, particularly for preterm and low-birth-weight infants who often require specialized care in a Neonatal Intensive Care Unit (NICU). Preterm birth, neonatal infections, respiratory disorders and other neonatal complications are important contributors to morbidity and mortality and frequently require pharmacological treatment. [1,2] The use of medicines in neonates is challenging because physiological processes such as drug absorption, distribution, metabolism and excretion differ considerably from those in older children and adults. Factors such as gestational age, birth weight and the maturity of various organs can influence drug dosing, response and safety. In addition, information on the safety, efficacy and appropriate dosing of many medicines in neonates is still limited. Therefore, appropriate and rational use of medicines is particularly important in the NICU. [3,4] Neonates admitted to the NICU may require several medicines depending on their clinical condition. Common indications include infections, respiratory disorders, apnea of prematurity, seizures and other neonatal complications. Antimicrobials are among the most frequently prescribed medicines in neonatal units, while surfactants and caffeine are commonly used in selected preterm infants with respiratory disorders and apnea of prematurity. [5,6] The number and type of medicines prescribed may differ according to gestational age, birth weight, clinical condition, referral pattern and prescribing practices followed at individual institutions. Drug utilization research provides a systematic way of assessing the extent and pattern of medicine use and helps identify commonly prescribed medicines and therapeutic groups, as well as variations in prescribing practices. A systematic review of drug-utilization studies in neonates reported considerable variation in medicine use between neonatal units, with antimicrobials being among the most frequently prescribed therapeutic groups. Similarly, a global review found substantial differences in prescribing patterns across neonatal units and highlighted the importance of conducting institution-specific drug-utilization studies. [6-8] The World Health Organization Anatomical Therapeutic Chemical (ATC) classification system provides a standardized approach to classifying medicines according to their anatomical, therapeutic, pharmacological and chemical properties. In addition, selected WHO prescribing indicators can be used to describe important aspects of prescribing practices. Together, these methods provide a structured approach to studying medicine utilization and allow comparison of prescribing patterns across different healthcare settings. [9,10] Despite the available evidence, prescribing patterns in NICUs may differ between institutions because of variations in patient characteristics, disease profiles, treatment protocols and available resources. Therefore, hospital-based drug-utilization studies are important for understanding local prescribing practices and identifying areas that may require further evaluation. The present study was undertaken to assess the drug utilization patterns among neonates admitted to the Neonatal Intensive Care Unit of a tertiary-care hospital using the WHO Anatomical Therapeutic Chemical classification system and selected drug-utilization indicators.

Study Design and Setting A retrospective, observational, cross-sectional drug-utilization study was conducted to assess the pattern of medicines prescribed to neonates admitted to the Neonatal Intensive Care Unit (NICU) of Koppal Institute of Medical Sciences, Koppal during the study period. Ethical Considerations Prior to commencement of the study, approval was obtained from the Institutional Ethics Committee of Koppal Institute of Medical Sciences, Koppal . Permission was obtained from the relevant hospital authorities to access the neonatal medical records. Study Population The study population consisted of neonates admitted to the NICU during the study period who received at least one therapeutic medicine during their hospital stay. Inclusion Criteria • Records of neonates who received at least one therapeutic medicine during their hospital stay. • Records containing sufficient information regarding the medicines prescribed or administered. Exclusion Criteria • Records in which only supportive interventions such as intravenous fluids, oxygen therapy, phototherapy, blood products or vaccination were provided without any therapeutic medicine. • Records with insufficient information regarding drug utilization. Sample Size The sample size was calculated using the single population proportion formula: n = Z²pq / d² Where: n = required sample size Z = standard normal deviate at 95% confidence level = 1.96 p = anticipated proportion of neonates receiving antibiotics = 81.3% = 0.813 q = 1 − p = 0.187 d = absolute precision = 2.62% = 0.0262 Based on a previous drug-utilization study conducted in a tertiary-care neonatal intensive care unit in Mumbai, India, 81.3% of neonates received at least one antibiotic. This proportion was considered for sample-size estimation. [7] Therefore, n = (1.96)² × 0.813 × 0.187 / (0.0262)² n = 849.8 Thus, the minimum required sample size was rounded off to 850 neonates. Data Collection Data were collected retrospectively from neonatal medical records, treatment charts and medication records using a structured data collection proforma. Demographic data, data regarding diagnosis and drugs treatment were collected. All medicines identified in the neonatal records were classified according to the World Health Organization Anatomical Therapeutic Chemical (ATC) classification system and WHO-core prescribing indicators. Data Analysis Data were entered into Microsoft Excel and analyzed using SPSS 25. Categorical variables were expressed as frequencies and percentages. Continuous variables were summarized using mean, standard deviation and range, as appropriate

Table 1: Demographic and clinical characteristics of the neonates Variable Frequency, n (%) p-value Gender Male 442 (52.0) 0.246 Female 408 (48.0) Total 850 (100.0) Gestational age at birth ≥37 weeks 578 (68.0) <0.001 32–36 weeks 204 (24.0) 28–31 weeks 51 (6.0) <28 weeks 17 (2.0) Total 850 (100.0) Birth weight ≥2500 g 595 (70.0) <0.001 1500–2499 g 187 (22.0) <1500 g 51 (6.0) <1000 g 17 (2.0) Total 850 (100.0) Mode of delivery NVD 468 (55.0) <0.001 Cesarean section 382 (45.0) Total 850 (100.0) Mode of discharge Discharged 765 (90.0) <0.001 Death 51 (6.0) DAMA 17 (2.0) Transfer 17 (2.0) Total 850 (100.0) A total of 850 neonates were included in the study. The demographic and clinical characteristics of the study population are presented in Table 1. There was a slight male predominance, with males accounting for 52.0% (n=442) and females for 48.0% (n=408). Most neonates were born at ≥37 weeks of gestation (68.0%, n=578), while 24.0% (n=204) were born at 32–36 weeks. Neonates born at 28–31 weeks and those born before 28 weeks accounted for 6.0% (n=51) and 2.0% (n=17), respectively. The majority of neonates having a birth weight of ≥2500 g (70.0%, n=595). Low birth weight was recorded in 22.0% (n=187), very low birth weight in 6.0% (n=51), and extremely low birth weight in 2.0% (n=17) of neonates. Normal vaginal delivery was slightly more common than cesarean delivery, accounting for 55.0% (n=468) and 45.0% (n=382), respectively. Most neonates were discharged from the hospital (90.0%, n=765). Death occurred in 6.0% (n=51) of cases, while 2.0% (n=17) were discharged against medical advice and another 2.0% (n=17) were transferred. Table 2: Morbidities observed among the study population Morbidity Frequency, n Percentage, % Respiratory distress syndrome (RDS) 493 58.0 Neonatal jaundice 383 45.0 Neonatal sepsis 255 30.0 Prematurity 213 25.0 Birth asphyxia 102 12.0 Infant of diabetic mother (IDM) 60 7.0 Hypoglycemia 51 6.0 Neonatal convulsions 34 4.0 Congenital anomalies 26 3.0 Necrotizing enterocolitis (NEC) 9 1.0 Total * 1,626 191.0 *The total exceeds 850 because neonates could have more than one morbidity. Therefore, this total should not be interpreted as the number of neonates. The morbidity profile of the cohort is shown in Table 2. Respiratory distress syndrome (RDS) was the most frequently recorded morbidity, affecting 58.0% (n=493) of neonates. Neonatal jaundice was reported in 45.0% (n=383), followed by neonatal sepsis in 30.0% (n=255) and prematurity in 25.0% (n=213). Other reported morbidities included birth asphyxia (12.0%, n=102), infant of diabetic mother (7.0%, n=60), and hypoglycaemia (6.0%, n=51). Neonatal convulsions were recorded in 4.0% (n=34) of neonates, while congenital anomalies were reported in 3.0% (n=26). Necrotizing enterocolitis was the least frequently reported condition, occurring in 1.0% (n=9) of neonates. Table 3: Distribution of prescribed drugs according to WHO-ATC classification (N = 2,125) WHO-ATC category Frequency, n Percentage, % Respiratory system 893 42.0 Anti-infective 595 28.0 Nervous system 319 15.0 Cardiovascular system 170 8.0 Alimentary tract 85 4.0 Others 63 3.0 Total 2,125 100.0 A total of 2,125 medicines were prescribed during the study period. Their distribution according to the WHO Anatomical Therapeutic Chemical (ATC) classification is presented in Table 3. Medicines classified under the respiratory system constituted the largest category, accounting for 42.0% (n=893) of all medicines prescribed. Anti-infective medicines were the second most frequently represented category, accounting for 28.0% (n=595). Medicines acting on the nervous system accounted for 15.0% (n=319) of prescriptions, followed by cardiovascular medicines at 8.0% (n=170). Medicines belonging to the alimentary tract accounted for 4.0% (n=85), while the remaining 3.0% (n=63) were classified under other categories. Table 4: Distribution of drugs prescribed according to WHO-ATC code Drug category ATC code Drug Neonates, n Percentage, % Respiratory system R07AA Surfactant 320 37.6 R03DA05 Aminophylline 210 24.7 R03BB01 Ipratropium bromide (nebulizer) 150 17.6 R03BA02 Budesonide (nebulizer) 90 10.6 Anti-infective J01CA01 Ampicillin 240 28.2 J01GB03 Gentamicin 200 23.5 J01DD01 Cefotaxime 130 15.3 J01CF02 Cloxacin 60 7.1 J01XA01 Vancomycin 40 4.7 J01DH02 Meropenem 25 2.9 J01GB06 Amikacin 20 2.4 J01XD01 Metronidazole 10 1.2 J02AC01 Fluconazole 8 0.9 J01MA02 Ciprofloxacin 5 0.6 Central nervous system N06BC01 Caffeine citrate 260 30.6 N03AA02 Phenobarbital 110 12.9 N02BE01 Paracetamol 45 5.3 N05CD08 Midazolam 35 4.1 N01AH01 Fentanyl 20 2.4 N03AB02 Phenytoin 15 1.8 N02AA01 Morphine 10 1.2 Cardiovascular system C01CA04 Dopamine 75 8.8 C03CA01 Furosemide 55 6.5 C01CA24 Adrenaline 15 1.8 C01CA07 Dobutamine 8 0.9 C02DB02 Hydralazine 4 0.5 Alimentary tract A02BC01 Omeprazole 30 3.5 A03FA03 Domperidone 12 1.4 Endocrine system H02AB09 Hydrocortisone 18 2.1 Others — Supplement 46 5.4 The individual drugs prescribed within each therapeutic category are presented in Table 4. Among respiratory medicines, surfactant was the most frequently prescribed agent (n=320, 37.6%), followed by aminophylline (n=210, 24.7%), ipratropium bromide administered by nebulization (n=150, 17.6%), and budesonide administered by nebulization (n=90, 10.6%). Ampicillin was the most frequently prescribed anti-infective medicine (n=240, 28.2%), followed by gentamicin (n=200, 23.5%) and cefotaxime (n=130, 15.3%). Other anti-infective medicines were prescribed less frequently, including cloxacillin, vancomycin, meropenem, amikacin, metronidazole, fluconazole, and ciprofloxacin. Within the central nervous system category, caffeine citrate was the most frequently prescribed drug (n=260, 30.6%), followed by phenobarbital (n=110, 12.9%) and paracetamol (n=45, 5.3%). Midazolam, fentanyl, phenytoin, and morphine were prescribed less frequently. Among cardiovascular medicines, dopamine was the most commonly prescribed drug (n=75, 8.8%), followed by furosemide (n=55, 6.5%). Adrenaline, dobutamine, and hydralazine accounted for smaller proportions of prescriptions. Omeprazole and domperidone were the reported medicines under the alimentary tract category, while hydrocortisone represented the endocrine-system medicines. Supplements accounted for 5.4% (n=46) of the prescriptions. Table 5: Prescribing pattern based on WHO core indicators WHO core indicator Value Total number of drugs prescribed 2,125 Average number of drugs per neonate 2.5 Prescriptions including antibiotics 45.0% Prescriptions given by injection 60.0% Drugs from the modeled essential medicines list 90.0% The prescribing indicators are summarized in Table 5. Across the study cohort, 2,125 medicines were prescribed, giving an average of 2.5 medicines per neonate. Antibiotics were included in 45.0% of prescriptions, while 60.0% of prescriptions involved injectable medicines. In addition, 90.0% of the prescribed medicines were reported to be included in the modeled essential medicines list.

This cross-sectional study of 850 neonates describes prescribing patterns in the NICU of a tertiary-care teaching hospital and contributes to institution-specific drug-utilization data from neonatal units in India. In the present study, most neonates were term (≥37 weeks, 68.0%) and had normal birth weight (≥2500 g, 70.0%). This differed from Chauthankar et al., where 54.8% were preterm and 73% had low birth weight. [7] Jayaram et al. reported 29.7% preterm neonates, with neonatal sepsis as the leading admission diagnosis. [8] The lower proportion of preterm and low-birth-weight neonates in our study may partly explain the lower average number of medicines prescribed. Respiratory distress syndrome (58.0%) was the most common diagnosis, followed by jaundice (45.0%) and neonatal sepsis (30.0%). This differed from studies in which sepsis predominated; Jayaram et al. reported neonatal sepsis in 37.9% of admissions, [8] while a Libyan NICU study reported 87.5%. The difference in case-mix was reflected in drug utilization, with respiratory-system medicines (42.0%) being the most frequently used ATC category, followed by anti-infectives (28.0%). In comparison, anti-infectives accounted for 60.36% of prescriptions in the Southern Karnataka cohort [8] and approximately 80% in the Libyan cohort. The frequent use of surfactant, aminophylline and nebulized bronchodilators was consistent with the predominance of respiratory disorders and established neonatal treatment practices. [5,6] Ampicillin, gentamicin and cefotaxime were the most commonly prescribed anti-infectives, similar to findings reported by Chauthankar et al. [7] and Warrier et al. [11]. The use of ampicillin with gentamicin as empirical therapy is consistent with commonly followed approaches for suspected neonatal sepsis. The average number of medicines prescribed per neonate was 2.5, lower than the 5.7 reported by Chauthankar et al., 3.57 by Jayaram et al. and 2.9 in the Libyan study [7,8]. This may be related to the lower proportion of extremely preterm and extremely low-birth-weight neonates in our cohort. Antibiotics were prescribed to 45.0% of neonates, compared with 81.3% reported by Chauthankar et al. [7] The lower antibiotic use may reflect the lower sepsis burden in our study, indicating that antibiotic-use rates should be interpreted in relation to case-mix. Adherence to the Essential Medicines List was high, with 90.0% of prescribed medicines included in the relevant list, comparable with the 97.4% reported in the Libyan NICU study. [9,10]. Off-label and unlicensed medicine use was not assessed in the present study but remains relevant in neonatal pharmacotherapy. Previous studies reported off-label prescribing in 12.3% of drugs and 38% of neonates in a Mumbai cohort [7], 43% of prescriptions in a South Indian NICU, and 34–39% in a German NICU [12], with similar concerns reported from Iranian NICUs [13]. Future studies could therefore assess off-label and unlicensed medicine use in our setting. Overall, drug utilization was influenced by the clinical profile of admitted neonates, referral patterns and institutional practices. Although the distribution of therapeutic groups differed from some previous studies, treatments such as ampicillin-gentamicin for suspected sepsis, surfactant for respiratory distress and caffeine for apnea of prematurity remain consistent with established neonatal practice. [3,4,6,7,8,11] Institution-specific audits remain useful for monitoring prescribing and identifying areas for improvement, particularly antimicrobial stewardship, injectable medicine use and off-label prescribing. [9,10] The study has certain limitations. Its retrospective design depended on the completeness and legibility of medical records, and dosing appropriateness, treatment duration and adverse drug events were not assessed. However, the relatively large sample size of 850 neonates compared with most published Indian NICU studies involving approximately 80–460 neonates [7,8] is a strength and provides greater precision in describing drug-utilization patterns.

The present study highlights the pattern of medicine use among neonates admitted to the NICU of a tertiary-care teaching hospital. Respiratory-system medicines were the most commonly used therapeutic group, which was consistent with the high proportion of neonates admitted with respiratory distress. Anti-infectives were also frequently prescribed, with ampicillin, gentamicin and cefotaxime being the commonly used agents. The average number of medicines prescribed per neonate was lower than that reported in several previous studies, which may be related to differences in the clinical profile of the study population. Injectable medicine use was also lower than that reported in some other NICU settings, while adherence to the Essential Medicines List was high. Overall, the findings show that prescribing patterns were influenced by the clinical conditions of the neonates and institutional practices. Regular drug-utilization reviews can help monitor prescribing, promote rational medicine use and support better antimicrobial stewardship in neonatal care.

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