Published online Mar 9, 2026. doi: 10.5409/wjcp.v15.i1.111423
Revised: July 9, 2025
Accepted: October 21, 2025
Published online: March 9, 2026
Processing time: 250 Days and 13.9 Hours
Neonatal sepsis continues to remain a serious threat, with multiple maternal and neonatal risk factors. Understanding these determinants will empower clinicians in comparable settings to apply targeted interventions, ultimately reducing new
To assess maternal and infant risk factors, the aim is to develop evidence-based strategies for preventing neonatal sepsis.
A total of 453 neonates and their mothers were enrolled, of which 146 were cases. Clinical, demographic, and obstetric data were analyzed including maternal in
Male sex (adjusted odd ratio [AOR] = 1.9; 95% confidence interval [CI]: 1.03-3.5), forceps-assisted vaginal delivery (AOR = 3.4; 95%CI: 1.1-14.9), fewer than four antenatal care visits (AOR = 2.9; 95%CI: 1.4-6.5), prolonged labor > 24 hours (AOR = 6.2; 95%CI: 2.8-17), rupture of membranes > 18 hours (AOR = 3.0; 95%CI: 1.6-6.8), and maternal urinary tract infection (AOR = 3.5; 95%CI: 2.4-29.4) significantly increased neonatal sepsis risk. Unclean vaginal examinations (AOR = 4.2; 95%CI: 1.6-11) and foul-smelling amniotic fluid (AOR = 10.3; 95%CI: 1.9-56.4) were among the strongest risk factors. Among neonatal factors prematurity (AOR = 4.3; 95%CI: 2.8-6.6), low birth weight ≤ 1500 g (AOR = 3.6; 95%CI: 2.2-5.7), birth asphyxia (AOR = 4.3; 95%CI: 2.4-7.6), and small-for-gestational-age status (AOR = 2.1; 95%CI: 1.1-4) were significant predictors. Respiratory support showed a strong correlation, with surfactant administration (AOR = 9.7; 95%CI: 4.1-22.9), continuous positive airway pressure) (AOR = 15.4; 95%CI: 9.4-25.1), and invasive ventilation (AOR = 53; 95%CI: 12.7-89) as the highest risk factors. Extended newborn intensive care unit stays (> 7 days: AOR = 38.9; > 15 days: AOR = 30) further elevated the likelihood of sepsis, likely due to nosocomial exposure.
The findings highlight the importance of enhanced prenatal care, timely labor management, strict hygiene protocols, and focused neonatal monitoring to reduce neonatal sepsis incidence. Addressing modifiable risk factors, including maternal infections and respiratory interventions, could significantly improve neonatal outcomes in resource-limited settings.
Core Tip: Neonatal sepsis in our study was strongly associated with several modifiable maternal and intrapartum factors, namely insufficient antenatal visits, prolonged labor or membrane rupture, forceps delivery, non-sterile vaginal examinations, and maternal urinary tract infections. Compounded by neonatal vulnerabilities including prematurity, very low birth weight, small-for-gestational-age, birth asphyxia, advanced respiratory support need, prolonged newborn intensive care unit (NICU) stays, with the latter reflecting greater exposure to nosocomial pathogens. Targeted, tiered interventions spanning antenatal care through delivery and the NICU, emphasizing risk stratification, aseptic practices, early surveillance, and timely prophylaxis can sharply reduce sepsis rates and enhance newborn survival.
- Citation: Qureshi MA, Sood M, Thakur P, Sood I. Maternal and neonatal determinants of newborn sepsis: A case-control study in resource-limited settings. World J Clin Pediatr 2026; 15(1): 111423
- URL: https://www.wjgnet.com/2219-2808/full/v15/i1/111423.htm
- DOI: https://dx.doi.org/10.5409/wjcp.v15.i1.111423
Despite substantial progress in reducing under-five mortality, neonatal mortality remains alarmingly high worldwide, with an estimated four million neonatal deaths occurring annually, 98% of which take place in developing nations[1]. Neonatal sepsis is a major contributor to these deaths, particularly in low- and middle-income countries[2]. In India alone, approximately 17000 cases of neonatal sepsis are reported per 100000 live births, with a case fatality rate ranging from 25% to 65%[3]. This life-threatening systemic infection may be either clinically suspected or confirmed through cultures. Common presentations include septicemia, meningitis, pneumonia, arthritis, and urinary tract infections (UTIs). Evidence suggests that risk-based screening and prompt treatment initiation significantly reduce the morbidity and mortality associated with neonatal sepsis[4].
Neonatal sepsis results from a combination of maternal and neonatal risk factors, including prematurity, male sex, cesarean delivery, intrapartum fever, instrumental delivery, multiple vaginal examinations during labor, and inadequate antenatal care (ANC)[5]. Its epidemiology is further shaped by regional pathogen profiles and antimicrobial resistance patterns, which vary significantly across different areas. In some regions, high resistance rates to commonly used antibiotics pose a serious challenge to effective treatment[5]. This variability necessitates the need for region-specific studies to identify causative factors, predominant pathogens, resistance trends, and gaps in diagnosis and treatment which can be used to formulate targeted antibiotic therapy and other management strategies.
Recognizing the limited region-specific data on neonatal sepsis risk factors in resource-constrained, high-altitude rural-tertiary hospital, this study was conducted at the public referral newborn unit in Shimla, Himachal Pradesh. Its primary objective was to identify determinants of neonatal sepsis through prevalent local epidemiological factors, including microbial profile and antibiotic-resistance pattern, facility infrastructure and quality of care. By utilizing the insights from this study, medical professionals in similar healthcare settings will be better equipped to combat neonatal sepsis effectively, ultimately improving newborn morbidity and mortality outcomes.
This research was conducted as an unmatched case-control study from August 2023 until July 2024 after approval from the institute ethical committee, at Kamla Nehru Hospital, Shimla, Himachal Pradesh. Prior informed written consent was taken from participants legal guardian before enrolment into the study.
The newborn unit functions as a referral and teaching hospital, providing diverse population representation for clinical research. The unit is manned by 3 physicians and 20 nurses, with 30 newborn intensive care unit (NICU) beds and annual admission of more than 1500, with sepsis accounting for more than 800 of those admissions. The study population comprised cases (neonates with sepsis) and control (neonates without sepsis) born in the hospital and admitted to the NICU during the study period. Cases were neonates with clinical signs and symptoms of possible serious bacterial infection, according to World Health Organization (WHO) Integrated Management of Neonatal and Childhood Illness guidelines[6], as the presence of any one of seven (difficulty feeding, history of convulsions, movement only when stimulated, respiratory rate of 60 or more breaths per min, severe chest retractions, or a temperature of 37.5 °C or higher or 35.5 °C or lower and change in level of activity); along with ≥ 2 of the hematological criteria, total leukocyte count
From a previous study, the proportion of women with UTI among controls delivered in health facility was 8.3% compared to 26.9% among cases. Using the Epi info software, setting ratio of controls to cases at 4:1 with 95% confidence interval (CI) and 80% power, total 453 neonates were included, 146 (32.2%) cases with sepsis and 307 (67.8%) controls.
Data related to maternal and neonatal risk factors, laboratory parameters, and culture reports were meticulously extracted from the hospital records by principal investigator in Microsoft Excel prepared after reviewing literature and checklists related to risk factors of neonatal sepsis. Continuous follow up and supervision was made for data completeness, clarity, consistency and accuracy by the supervisor throughout the study.
Data were exported to STATA version 14 for analysis. The dependent variable was neonatal sepsis, and independent variables were newborn and maternal variables studied. Descriptive statistics were used to assess the sociodemographic characteristics of the mother and neonates, and the result was summarized as frequencies and percentages. χ² and odds ratio (OR) were used to assess the relationship between factors associated with the occurrence of neonatal sepsis. Then variables that had association in the bivariate model (P < 0.25) were entered and analyzed by a multivariable logistic regression model to identify the independent effect of different factors for occurrence of sepsis. Collinearity among predictors was assessed, and when any pair showed a Pearson r > 0.80, the variable with lesser clinical relevance was excluded. Statistical significance was declared at P < 0.05. The result was reported using crude and adjusted OR (AOR) with their 95%CI.
Among total 453 neonates enrolled with their mothers, 260 (57.4%) were males. There were 146 cases, of which a higher proportion was male (65.8%). The mean gestation of neonates was 36.5 weeks (± 2.1). Fast breathing (37.0%) and chest indrawing (32.9%) were the most frequently observed symptoms, whereas lethargy (13.7%), jaundice (14.4%), and poor feeding (8.2%) were also notable. Fever (≥ 38 °C) occurred in 13.7% of cases, whereas hypothermia (≤ 36.5 °C) was recorded in 4.8%. Apnea (8.2%) and convulsions (6.8%) were present, with congenital anomalies identified in 2.1% of cases. Additionally, 28.1% presented with various symptoms that were not separately classified.
The mean maternal age was 27.2 years (standard deviation ± 5.4). Caesarean births accounted for 45.7% of deliveries. No significant difference was observed in the mode of delivery between cases (50.7% vaginal, 49.3% caesarean) and controls (51.8% vaginal, 48.2% caesarean). However, forceps-assisted deliveries were notably higher among cases (21.3%) compared to controls (0.7%). Maternal education was higher in the control group, and a greater proportion of septic neonates (21.9%) were born to mothers with no formal education. A higher number of ANC visits was associated with a lower likelihood of neonatal sepsis. Prolonged labor exceeding 24 hours was significantly more common in cases (15.8%) than controls (2.3%). Similarly, membrane rupture lasting more than 18 hours was reported in 16.4% cases vs 4.9% controls; 48.6% had < 6 hours duration of rupture of membranes, followed by 6-12 hours in 36.6%. UTI was present in 11% of mothers with septic infants, compared to only 1% in controls. Among cases, unclean vaginal examinations were reported in 34.9% of mothers, foul-smelling discharge in 25.3%, and meconium-stained amniotic fluid in 22.6%, which were all notably higher than in the control group. Table 1 summarizes the descriptive statistics of maternal factors associated with neonatal sepsis.
| Total (n = 453) | Case (n = 146) | Control (n = 307) | P value | Crude odds ratio with 95%CI | AOR with 95%CI | |
| Sex | ||||||
| Female | 193 (42.6) | 50 (34.2) | 143 (46.6) | 0.013 | 1.6 (1.13-2.48) | 1.9 (1.03-3.5) |
| Male | 260 (57.4) | 96 (65.8) | 164 (53.4) | |||
| Place of delivery | ||||||
| Clean labor room | 233 (51.4) | 74 (50.7) | 159 (51.8) | 0.917 | 1.4 (0.2-8.7) | |
| Operation theater | 220 (48.6) | 72 (49.3) | 148 (48.2) | |||
| Assisted vaginal delivery | ||||||
| No | 420 (92.7) | 115 (78.7)) | 305 (99.3) | 0.02 | 4.8 (1.1-20.5) | 3.4 (1.1-14.9) |
| Forceps | 33 (7.3) | 31 (21.3) | 2 (0.7) | |||
| Maternal age in years | 27.2 ± 5.4 | 26.7 ± 5.4 | 27.4 ± 5.3 | 0.16 | 0.98 (0.94-1.02) | |
| Maternal education | ||||||
| Uneducated | 75 (16.6) | 32 (21.9) | 43 (14) | |||
| Matric | 182 (40.2) | 70 (47.9) | 112 (36.5) | 0.14 | 1.5 (0.8-2.5) | 1.5 (0.6-2.1) |
| High school | 138 (30.5) | 36 (24.7) | 102 (33.2) | 0.003 | 2.4 (1.3-4.4) | 2.0 (1.0-3.9) |
| Graduate and above | 58 (12.8) | 8 (5.5) | 50 (16.3) | < 0.01 | 4.4 (1.8-10.8) | 3.1 (1.1-8.2) |
| Maternal parity | ||||||
| Primigravida | 167 (36.8) | 57 (39) | 110 (37) | 0.36 | 1.15 (0.76-1.72) | |
| Multigravida | 286 (63.2) | 89 (61) | 197 (63) | |||
| ANC visits | ||||||
| < 4 | 46 (10.2) | 29 (19.9) | 17 (5.5) | < 0.01 | 4.2 (2.2-7.9) | 2.9 (1.4-6.5) |
| ≥ 4 | 407 (89.8) | 117 (80.1) | 290 (94.5) | |||
| < 8 | 447 (98.3) | 145 (99.3) | 302 (98.4) | 0.42 | 0.4 (0.04-3.6) | |
| ≥ 8 | 6 (1.3) | 1 (0.7) | 5 (1.6) | |||
| Duration of labor in hours | ||||||
| < 24 | 414 (91.4) | 123 (84.2) | 300 (97.7) | < 0.01 | 8.0 (3.3-19.1) | 6.2 (2.8-17) |
| ≥ 24 | 30 (6.6) | 23 (15.8) | 7 (2.3) | |||
| Duration of rupture of membranes in hours | ||||||
| < 18 | 414 (91.4) | 122 (83.6) | 292 (95.1) | < 0.01 | 3.8 (1.9-7.5) | 3.1 (1.6-6.8) |
| ≥ 18 | 39 (8.6) | 24 (16.4) | 15 (4.9) | |||
| UTI in mother | ||||||
| Yes | 19 (4.2) | 16 (11) | 3 (1) | < 0.01 | 12.5 (3.57-43.5) | 3.5 (2.4-29.4) |
| No | 434 (95.8) | 130 (89) | 304(99) | |||
| Unclean vaginal examination | ||||||
| Yes | 62 (13.7) | 51 (34.9) | 11 (3.6) | < 0.01 | 14.4 (7.24-28.8) | 4.2 (1.6-11) |
| No | 391 (86.3) | 95 (65.1) | 296 (96.4) | |||
| Foul smelling liquor | ||||||
| Yes | 40 (8.7) | 37 (25.3) | 3 (1) | < 0.01* | 34.4 (10.4-114) | 10.3 (1.9-56.4) |
| No | 413 (91.3) | 109 (74.7) | 304 (99) | |||
| Meconium stained liquor | ||||||
| Yes | 83 (18.3) | 33 (22.6) | 50 (16.3) | 0.1 | 1.5 (0.9-2.4) | |
| No | 370 (81.7) | 113 (77.4) | 257 (83.7) | |||
Sepsis was notably higher among preterm below 34 weeks (57.6%); among those with BW of ≤ 1500 g (22.6%). Additionally, 58.9% of cases had a BW < 2500 g vs 23.8% with BW ≥ 2500 g. While 93.2% of controls had an appropriate BW for gestational age (GA), small for GA (SGA) neonates were more frequent in cases (13.7% vs 6.8%), suggesting a link between growth restriction and increased sepsis risk. Birth asphyxia was significantly more common in cases (26.0%), bag-and-mask ventilation was required more often in cases (63.2%) compared to controls (56.5). Similarly, intubation was slightly more frequent in cases (31.5%) than controls (26.1%), but no strong correlation was found (P = 0.2). A low APGAR score (≤ 3) at 5 minutes was observed in 42.1% cases compared to 26.1% controls, although the statistical significance remained weak. Hypoxic ischemic encephalopathy was observed in 8 (22%) of cases, and none in the control. Continuous positive airway pressure (CPAP) respiratory support was required in 67.1% of cases compared to only 11.7% of controls. Median duration on CPAP was 48 hours (range 6-384). Cases had longer duration of CPAP support compared to control, and 26% of neonates with sepsis required invasive ventilation compared to 0.7% of the control. Descriptive statistics of neonatal factors observed in septic neonates presented in Table 2.
| Total (n = 453) | Case (n = 146) | Control (n = 307) | P value | COR with 95%CI | AOR with 95%CI | |
| Gestation | ||||||
| Preterm | 157 (34.7) | 84 (57.6) | 73 (23.8) | < 0.01 | 4.9 (1.6-8.2) | 4.3 (2.8-6.6) |
| Term | 296 (65.3) | 62 (42.4) | 234 (76.2) | |||
| Birth weight in grams | ||||||
| ≤ 1500 | 50 (11) | 33 (22.6) | 17 (3.8) | < 0.01 | 4.6 (1.2-7.2) | 3.6 (2.2-5.7) |
| > 1500 | 403 (89) | 113 (77.3) | 290 (94.5) | |||
| < 2500 | 159 (35.1) | 86 (58.9) | 73 (23.8) | < 0.01 | 3.2 (1.0-6.3) | 2.2 (1.0-4.4) |
| ≥ 2500 | 294 (64.9) | 60 (41.1) | 234 (76.2) | |||
| Birth weight centile | ||||||
| Appropriate for gestation | 412 (93.4) | 126 (86.3) | 286 (93.2) | < 0.01 | 3.7 (1.01-5.1) | 2.1 (1.1-4) |
| Small for gestation | 41 (9.1) | 20 (13.7) | 21 (6.8) | |||
| Birth asphyxia | ||||||
| No | 392 (86.5) | 108 (74.0) | 284 (92.5) | < 0.01 | 5.2 (3.1-7.2) | 4.3 (2.4-7.6) |
| Yes | 61 (13.5) | 38 (26.0) | 23 (7.5) | |||
| Resuscitation details | ||||||
| Initial steps only | 6 (9.8) | 2 (5.3) | 4 (17.4) | |||
| Bag and mask | 37 (60.7) | 24 (63.2) | 13 (56.5) | 0.14 | 0.24 (0.04-1.6) | |
| Intubation | 18 (29.5) | 12 (31.5) | 6 (26.1) | 0.2 | 0.27 (0.03-1.95) | |
| APGAR at 5 minutes | ||||||
| ≤ 3 | 22 (36.1) | 16 (42.1) | 6 (26.1) | 0.2 | 2.06 (0.6-6.3) | |
| > 3 | 39 (63.9) | 22 (57.9) | 17 (73.9) | |||
| Surfactant given | ||||||
| Yes | 34 (7.5) | 27 (18.5) | 7 (2.3) | < 0.01 | 11.1 (3.7-26.8) | 9.7 (4.1-22.9) |
| No | 419 (92.5) | 119 (81.5) | 300 (97.7) | |||
| CPAP required | ||||||
| Yes | 134 (29.6) | 98 (67.1) | 36 (11.7) | < 0.01 | 18.4 (10.1-28.3) | 15.4 (9.4-25.1) |
| No | 319 (70.4) | 48 (32.9) | 271 (88.3) | |||
| Duration for CPAP in hours | ||||||
| > 96 | 84 (62.7) | 60 (64.5) | 24 (58.5) | 0.5 | 1.28 (0.6-2.7) | |
| ≤ 96 | 50 (37.3) | 33 (35.5) | 17 (41.5) | |||
| Invasive ventilation required | ||||||
| Yes | 40 (8.8) | 38 (26) | 2 (0.7) | < 0.01 | 58.1 (12-89.8) | 53 (12.7-89) |
| No | 413 (91.2) | 108 (74) | 305 (99.3) | |||
| Apnea | ||||||
| Yes | 27 (6) | 26 (17.8) | 1 (0.3) | < 0.01 | 5.1 (2.6-15) | 4 (2.8-12.9) |
| No | 426 (94) | 120 (82.2) | 306 (99.7) | |||
| Total SNCU stay in days | ||||||
| < 3 | 204 (45) | 9 (6.2) | 195 (63.5) | < 0.001 | 15.2 (3.6-55) | 12.9 (10-53.2) |
| ≥ 3 | 249 (54.9) | 137 (93.8) | 112 (36.5) | |||
| < 7 | 305 (67.3) | 28 (19.2) | 277 (90.2) | < 0.001 | 42 (1.1-99.9) | 38.9 (22.2-68) |
| ≥ 7 | 148 (32.7) | 118 (80.8) | 30 (9.8) | |||
| < 15 | 374 (82.5) | 76 (52) | 298 (97) | < 0.001 | 38.1 (1.1-99.9) | 30 (14.5-63.8) |
| ≥ 15 | 79 (17.5) | 70 (48) | 9 (3) | |||
Multivariable logistic regression analysis identified several significant risk factors associated with neonatal sepsis. Findings indicate that male sex (AOR = 1.9; 95%CI: 1.03-3.5), assisted forceps vaginal delivery (AOR = 3.4; 95%CI: 1.1-14.9), and mothers with lower education had higher odds of neonates with sepsis, with an AOR = 2 (95%CI: 1.0-3.9) compared to high school and 3.1 (95%CI: 1.1-8.2) compared to graduates. Additionally, having fewer than four ANC visits (AOR = 2.9; 95%CI: 1.4-6.5) was associated with elevated risk.
Labor-related risk factors include prolonged labor exceeding 24 hours (AOR = 6.2; 95%CI: 2.8-17) and rupture of membranes more than 18 hours (AOR = 3.1; 95%CI: 1.6-6.8). Maternal health and procedural factors also played a role, as the presence of maternal UTI (AOR = 3.5; 95%CI: 2.4-29.4), unclean vaginal examinations (AOR = 4.2; 95%CI: 1.6-11), and foul-smelling amniotic fluid (AOR = 10.3; 95%CI: 1.9-56.4) were all significantly associated with an increased likelihood of neonatal sepsis.
Newborn factors significantly associated with sepsis include prematurity (AOR = 4.3; 95%CI: 2.8-6.6) and LBW (≤ 1500 g: AOR = 3.6; 95%CI: 2.2-5.7; < 2500 g: AOR = 2.2; 95%CI: 1.0-4.4). SGA neonates also demonstrated increased risk (AOR = 2.1; 95%CI: 1.1-4). Birth asphyxia emerged as a strong predictor (AOR = 4.3; 95%CI: 2.4-7.6). Among neonates requiring respiratory support, surfactant administration was associated with a notably high sepsis risk (AOR = 9.7; 95%CI: 4.1-22.9). CPAP for respiratory distress increased odds for sepsis 15.4 times (95%CI: 9.4-25.1), while invasive ventilation posed the highest risk (AOR = 53; 95%CI: 12.7-89), reflecting the severity of neonatal illness. Apnea showed a strong correlation (AOR = 4; 95%CI: 2.8-12.9), while extended NICU stay (> 7 days: AOR = 38.9; > 15 days: AOR = 30) substantially in
Neonatal sepsis continues to remain a significant global health concern and contribute to substantial neonatal morbidity and death worldwide, a burden that is especially severe in developing countries and in resource-constrained settings such as ours. In a tertiary care hospital in north India, we investigated the epidemiological profile and the maternal and neonatal determinants linked to sepsis in newborns. Our analysis identified key contributors including maternal health status, delivery circumstances, birth characteristics, and early neonatal interventions that markedly increase the risk of sepsis. By pinpointing these factors, clinicians can devise targeted prevention and management strategies to reduce avoidable risks and enhance neonatal survival.
We observed sepsis in 32.2% of neonates, with a clear male predominance (65.8%), reflecting a substantial burden in our setting. These figures align with Jabiri et al[7], who reported a 31.4% prevalence, and Katugume et al[8] who reported in 41.2%, highlighting persistently high incidence rates in resource-limited health facilities. The male bias likely stems from inherent biological, genetic, and immunological disparities between sexes. Clinically, tachypnea and chest indrawing were the most frequent signs, followed by lethargy, jaundice, and feeding difficulties, findings that mirror those of Jatsho et al[9].
Multiple maternal factors were strongly linked to neonatal sepsis, reinforcing the importance of prenatal care, delivery practices, and intrapartum hygiene protocols. In our cohort, 22% of septic neonates were born to mothers without formal schooling, and low maternal education emerged as an independent risk factor likely reflecting gaps in health literacy, hygiene practices, care-seeking behavior, and facility access as observed by Kayom et al[10] and Nigatu et al[11]. Women with fewer than four antenatal visits faced 2.9-fold higher odds of delivering a septic neonate, reaffirming that ANC permits undiagnosed infections and obstetric complications[12], in line with WHO guidance[13].
Instrumental vaginal delivery specifically forceps assistance was associated with a 3.4-fold increase in sepsis risk, reflecting the trauma and bacterial colonization inherent to such procedures as observed by Maisaba et al[14]. Although caesarean sections comprised 48.6 percent of births, they did not differ significantly between cases and controls; however, study by Puopolo et al[15] suggested elective caesarean may protect against early-onset sepsis.
Prolonged labor exceeding 24 hours raised the sepsis risk six-fold (AOR = 6.2; 95%CI: 2.8–17), while membrane rupture more than 18 hours tripled the odds (AOR = 3.1; 95%CI: 1.6–6.8), both reflecting greater opportunity for ascending pathogens into the uterine cavity, increasing neonatal exposure to pathogens during delivery in line with findings from earlier studies[16,17].
Maternal UTI conferred a 3.5-fold higher risk of neonatal sepsis (95%CI: 2.4–29.4), illustrating vertical bacterial transmission during labor[18]. Unclean vaginal examination (AOR = 4.2; 95%CI: 1.6–11) and foul-smelling amniotic fluid (AOR = 10.3; 95%CI: 1.9–56.4) emphasized how lapses in delivery-room hygiene facilitate intrapartum infections. Echoing studies from Ghana and other hospitals in India[19,20], these findings highlight that suboptimal intrapartum care directly increases neonatal pathogen exposure and sepsis risk.
Preterm neonates (< 34 weeks) and those with LBW (< 2500 g, especially < 1500 g) were significantly over represented among sepsis cases. In multivariable analysis, prematurity (AOR = 4.3, 95%CI: 2.8-6.6) and BW ≤ 1500 g (AOR = 3.6; 95%CI: 2.2-5.7) emerged as independent predictors. These neonates are known to have underdeveloped immune systems and skin/mucosal barriers, with prolonged hospital stay increasing their susceptibility. Our findings agree with global and national studies[20,21]. SGA status also showed an elevated sepsis risk (AOR = 2.1; 95%CI: 1.1-4), likely reflecting chronic intrauterine compromise, suboptimal placental function, and metabolic vulnerability. which collectively increase susceptibility to infections[22,23].
Birth asphyxia (AOR = 4.3; 95%CI: 2.4-7.6) remained a critical predictor, consistent with research showing that hypoxic stress disrupts neonatal immune response, facilitating bacterial invasion[20].
Our study uniquely highlights the very high risk posed by respiratory support. Surfactant administration (AOR = 9.7; 95%CI: 4.1-22.9) and CPAP requirement (AOR = 15.4; 95%CI: 9.4-25.1) indicated severe respiratory distress, further predisposing neonates to sepsis through prolonged oxygen dependency and device-associated infections as observed by Jovičić et al[23] Invasive ventilation (AOR = 53; 95%CI: 12.7-89) was the most significant risk factor, underscoring the heightened exposure to ventilator-associated pneumonia and prolonged hospital stay. These findings emphasize the dual nature of respiratory support in neonatology: While lifesaving, they may also be sources of nosocomial infections due to prolonged device use, invasive access, and biofilm formation on equipment. Similar associations have been observed by Haksari et al[22] and Sturrock et al[24].
Extended NICU stay (≥ 7 days: AOR = 38.9; ≥ 15 days: AOR = 30) amplified sepsis risk, reinforcing the need for strict infection control policies in neonatal intensive care units. Longer hospital stay likely reflect both the severity of illness and increased cumulative risk of nosocomial infection, as supported by Sturrock et al[24], from Ethiopia[21] and India[20]. Strict infection control and early discharge planning are essential strategies to reduce neonatal sepsis risk.
Set in a tertiary referral hospital and serving a predominantly rural, mountainous population, our facility recorded neonatal sepsis in 32.2 percent of admissions. The incidence of clinically suspected sepsis was 166.0 (95%CI: 97.69–234.24) per 1000 live births, laboratory-confirmed sepsis 46.9 (19.04–74.79) per 1000 live births, and all-cause mortality 0.83 (0.37–2.00) per 1000 neonate-days globally[25]. Although risk factors such as LBW and prematurity, and microbial profile (Gram-positive vs Gram-negative) are observed worldwide, their prevalence shifts with climate, socioeconomic status, and facility resources.
The major strength of our study lies in efficient and consistent selection of both cases and controls by enrolling neonates born within same hospital, a strategy bolstered by the high institutional delivery rate in our population. By applying both clinical and laboratory criteria including culture confirmation to define sepsis, we enhanced the accuracy and reliability of sepsis cases. Moreover, conducting this research in a predominantly rural, mountainous setting offers valuable insights into neonatal sepsis determinants within resource-constrained environments common to many low- and middle-income countries.
However, restricting enrolment to inborn neonates may have missed septic babies delivered outside our hospital, thereby limiting generalizability. The results are therefore most applicable to similar hospital settings and require adaptation for different demographic and microbial profiles, or healthcare infrastructures. Finally, the inherent nature of a hospital-based case–control design precludes direct causal association and further cohort studies, or randomized controlled trials are needed to validate the association between the identified risk factors and neonatal sepsis.
Given the strong associations between neonatal sepsis and maternal/neonatal risk factors, this study reinforces the need for early identification and targeted prevention to reduce neonatal sepsis burden. We propose a multi-pronged prevention strategy including improving ANC coverage to enable early maternal infection screening and prompt treatment, implement labor-management protocols that minimize prolonged labor and membrane rupture duration, enforcing strict aseptic technique for vaginal examinations and delivery procedures, providing intensified surveillance and early intervention for high-risk preterm, low-birth-weight, and growth-restricted infants and optimizing respiratory-support protocols in the NICU to reduce device-associated infections. By integrating these measures, we can target the key maternal and neonatal drivers of sepsis and substantially reduce its burden in resource-limited settings.
We would like to extend our heartfelt thanks for the study participants, their caregivers and data collectors who participated in the study. We are also thankful of the nurses of NICU who took care of sick neonates.
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