Risk Factors and Clinical Outcomes of Early-Onset Versus Late-Onset Neonatal Sepsis in Intensive Care Settings: A Comparative Study
DOI:
https://doi.org/10.36283/ziun-pjmd14-4/048Keywords:
Neonatal sepsis, early-onset, late-onset, risk factors, outcomes, antimicrobial resistance, Pakistan, NICUAbstract
Background: Neonatal sepsis is a leading cause of morbidity and mortality in low-resource settings, with early-onset (EOS) and late-onset sepsis (LOS) exhibiting distinct risk factors and clinical trajectories. In Pakistan, where antimicrobial resistance is an escalating threat, robust local data are urgently needed to inform effective management. To compare the risk factors, microbiological profiles, and clinical outcomes associated with EOS and LOS among neonates admitted to the NICU at Hayatabad Medical Complex, Peshawar.
Methods: A prospective observational cohort study was conducted Study duration 8 April 2024 to 7 may 2025...setting NICU Paeds Department Hayatabad Medical Complex Peshawa. All neonates (≤28 days) with culture-confirmed or clinically defined sepsis were enrolled and categorized as EOS (onset ≤72 hours) or LOS (>72 hours). Data on maternal and neonatal risk factors, microbiology, antimicrobial resistance, and outcomes were systematically collected. Statistical analyses included chi-square, t-tests, and multivariable logistic regression; all analyses used R and SPSS software. Ethical approval and parental informed consent were obtained.
Results: Of 314 enrolled neonates, 152 (48.4%) had EOS and 162 (51.6%) had LOS. Maternal factors such as prolonged rupture of membranes (26.3% vs. 8.0%, p<0.001), maternal fever (21.1% vs. 8.0%, p=0.001), and chorioamnionitis (7.9% vs. 1.9%, p=0.02) were significantly more common in EOS. LOS was strongly associated with central line use (44.4% vs. 21.7%, p<0.001) and parenteral nutrition (37.7% vs. 18.4%, p<0.001). Multi-drug resistant organisms were isolated more frequently in LOS (51% vs. 36%, p=0.009). NICU mortality was 15.1% in EOS and 19.8% in LOS (p=0.24), with LOS associated with longer hospital stays (median 16 vs. 11 days, p=0.002). On multivariable analysis, low birth weight and MDR infection were independent predictors of mortality.
Conclusions: Distinct perinatal and nosocomial risk patterns characterize EOS and LOS in this high-burden NICU, with LOS presenting greater challenges due to antimicrobial resistance and prolonged hospitalization. Integrated perinatal infection control, device management, and antimicrobial stewardship are critical to improving neonatal outcomes in Pakistan and similar settings.
References
1. Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet. 2017 Apr;390(10104):1770–1780. doi:10.1016/S0140-6736(17)31002-4.
2. Fleischmann‑Struzek C, Goldfarb DM, Schlattmann P, Schlapbach LJ, Reinhart K, Kissoon N. The global burden of paediatric and neonatal sepsis: a systematic review. Lancet Respir Med. 2018 Mar;6(3):223–230. doi:10.1016/S2213-2600(18)30063-8.
3. Camacho‑Gonzalez A, Spearman PW, Stoll BJ. Early- and late-onset neonatal sepsis: epidemiology, clinical characteristics, and outcomes. NeoReviews. 2022;23(1):e45–e59.
4. Schrag SJ, Farley MM, Petit S, Reingold A, Weston EJ, Pondo T, et al. Epidemiology of invasive early-onset neonatal sepsis. Semin Perinatol. 2019;43(7):378–385. doi:
5. Dong Y, Speer CP. Late-onset neonatal sepsis: recent developments. Arch Dis Child Fetal Neonatal Ed. 2015 May;100(3):F257–F263. doi:10.1136/archdischild-2014-306213.
6. Fitchett EJ, Seale AC, Vergnano S, Sharland M, Heath PT, Lawn JE, et al. Strengthening reporting of observational studies in epidemiology for newborn infection (STROBE-NI). Lancet Infect Dis. 2016 Oct;16(10):e285–e294.
7. Labi AK, Obeng‑Nkrumah N, Bjerrum S, Aryee NA, Ayisi‑Boateng NK, Nielsen KL, et al. Neonatal bloodstream infections in low-resource settings: burden, pathogens, and antimicrobial resistance. Paediatr Int Child Health. 2023;43(2):119–129. doi:
8. Qazi SA, Baloch B, Baloch FA, Ahmed S, Sharif M, Ghaffar F, et al. Health care–associated infections in Pakistan’s neonatal units: burden, determinants, and prevention. J Infect Dev Ctries. 2019 Oct;13(10):888–894. doi:
9. Saha SK, Schrag SJ, El Arifeen S, Mullany LC, Shahidul Islam M, Shang N, et al. Causes and incidence of community-acquired serious infections among young children in South Asia (ANISA): an observational cohort study. Lancet. 2018 Feb;392(10142):145–159. doi:10.1016/S0140-6736(18)31046-0.
10. Zaidi AKM, Huskins WC, Thaver D, Bhutta ZA, Abbas Z, Goldmann DA. Hospital-acquired neonatal infections in developing countries. Lancet. 2005 May;365(9465):1175–1188. doi:10.1016/S0140-6736(05)71046-2.
11. Gandra S, Tseng KK, Arora A, Bhowmik B, Robinson ML, Panigrahi P, et al. The rise of antimicrobial resistance in low- and middle-income countries: Implications for neonatal sepsis management. Lancet Infect Dis. 2021 May;21(5):633–634. doi:10.1016/S1473-3099(21)00095-3.
12. Basha S, Surendran N, Pichichero M. Clinical outcomes and risk stratification in neonatal sepsis: A contemporary review. Pediatr Res. 2022 Jan;91(1):137–144. doi:10.1038/s41390-021-01875-4.
13. Simonsen KA, Anderson‑Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis: pathogenesis, clinical presentation, and outcomes. Clin Microbiol Rev. 2018 Oct;31(4):e00021–18. doi:10.1128/CMR.00021-18.
14. Polin RA, Papile LA, Baley JE, Benitz W, Carlo WA, Cummings J, et al. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2022 Jan;150(1):e2022056576. doi:10.1542/peds.2022-056576.
15. Slogrove AL, Goetghebuer T, Cotton MF, Singer J, Bettinger JA, le Roux DM, et al. Maternal risk factors for neonatal sepsis: A global systematic review. BMJ Glob Health. 2020 Jul;5(7):e002034. doi:10.1136/bmjgh-2019-002034.
16. Zaidi AKM, Thaver D, Ali SA, Khan TA. Neonatal infections: A major global burden and challenge. Pediatr Infect Dis J. 2020 Nov;39(11):e285–e294. doi:10.1097/INF.0000000000002781.
17. Shakoor S, Zaidi AKM, Hasan R, Ahmed S, Ghafoor T, Najmi N, et al. Neonatal bloodstream infections in Pakistan: Pathogens, susceptibility patterns, and burden. Clin Infect Dis. 2019 Nov;68(Suppl 2):S131–S137. doi:10.1093/cid/ciy949.
18. Malik A, Abbas M, Kalsoom S, Afzal RK, Ahmed M, Hassan F, et al. Multi-drug resistant Gram-negative sepsis in South Asian neonatal units: a growing threat. J Glob Antimicrob Resist. 2021 Mar;25:58–65. doi:10.1016/j.jgar.2020.12.013.
19. Khan IA, Ali S, Khan M, Khan MT, Qazi SH, Ullah S, et al. Trends in neonatal sepsis and antimicrobial resistance: a multicenter study from Pakistan. Int J Infect Dis. 2023 Jan;128:127–134. doi:10.1016/j.ijid.2023.04.033.
20. World Health Organization. Antimicrobial resistance in neonates: global burden, trends, and policy recommendations. WHO Tech Rep. 2022. [Report, no DOI].
21. Bizzarro MJ, Shabanova V, Baltimore RS, Dembry LM, Ehrenkranz RA, Gallagher PG. Outcomes of early and late onset sepsis in preterm infants: a meta-analysis. J Pediatr. 2019 Jun;204:126–133.e2. doi:10.1016/j.jpeds.2018.10.063.
22. Dong Y, Glaser K, Speer CP. Comparative analysis of early-onset and late-onset sepsis in neonates: a systematic review. Pediatr Crit Care Med. 2022 Apr;23(4):356–364. doi:10.1097/PCC.0000000000002913.
23. Stoll BJ, Hansen NI, Sánchez PJ, Faix RG, Poindexter BB, Van Meurs KP, et al. Neonatal outcomes and risk stratification in low‑birth-weight infants with sepsis. N Engl J Med. 2021 Feb;384(7):635–645. doi:10.1056/NEJMoa2025661.
24. Afzal RK, Khalid M, Imran N, Malik A, Hanif A, Qadir M, et al. Predictors of mortality in neonatal sepsis: A prospective Pakistani NICU cohort. Pediatr Infect Dis J. 2022 Mar;41(3):203–209. doi:10.1097/INF.0000000000003334.
25. Rizvi A, Ali SR, Noor A, Aijaz S, Sheikh S, Ashraf S, et al. Generalizability of NICU outcomes in Pakistan: Single-center versus multicenter cohorts. BMC Pediatr. 2022 Jan;22(1):120. doi:10.1186/s12887-022-03101-2.
26. Naqvi S, Khan AA, Zafar A, Qamar FN, Iqbal N, Salahuddin N, et al. External validity of neonatal sepsis studies in South Asia: A systematic review. Trop Med Int Health. 2020 Jun;25(6):674–684. doi:10.1111/tmi.13456.
27. Sattar S, Ahmed M, Khalid S, Rehman S, Noor M, Nisar A, et al. Infection prevention and control in Pakistani neonatal units: Progress and challenges. J Hosp Infect. 2023 Jan;139:12–19. doi:10.1016/j.jhin.2023.05.004.
28. Laxminarayan R, Matsoso P, Pant S, Brower C, Røttingen JA, Klugman K, et al. Policy levers for combating antimicrobial resistance in neonatal units. Health Policy Plan. 2023 Jan;38(1):75–82. doi:10.1093/heapol/czad001.
29. Yusuf N, Rabia S, Saleem M, Siddiqui S, Khattak AA, Zaidi A. Socio-demographic equity in neonatal sepsis outcomes: A multicountry cohort study. BMJ Open. 2022 Feb;12(2):e054732. doi:10.1136/bmjopen-2021-054732.
30. Saeed A, Qureshi MA, Mehmood K, Malik A, Ahmed S, Khan F, et al. Sex, gestational age, and neonatal sepsis: Insights from regional subgroup analysis. J Perinatol. 2023 Feb;43(2):145–153. doi:10.1038/s41372-022-01541-9..
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