The Association between Birth Route and Early/Late onset Neonatal Sepsis in Term Infants: A Case-control Study in the NICU of a Tertiary Hospital in East Java, Indonesia

Document Type : Original Article

Authors

1 Department of Paediatrics, Faculty of Medicine Universitas Airlangga, Dr. Soetomo Hospital, Surabaya, Indonesia

2 Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia

Abstract

Background: In 2020, neonatal sepsis was recognized as the leading cause of neonatal death. The birth route can
affect the variety of microbial flora in neonates. Microbial colonization through the birth canal is vital to reduce
susceptibility to infection. This study aims to identify the association between the birth route and early and late-onset
neonatal sepsis in term infants.
Methods: This hospital-based case-control study was carried out on term infants diagnosed with neonatal sepsis at the
NICU of a tertiary referral hospital in East Java from 1 January 2019 to 31 December 2019. Preterm neonates were
excluded as they may be more likely to develop neonatal sepsis. The Chi-square test and odds ratio (OR) with a
confidence interval of 95% (CI=95%) were used to analyze data. P-value <0.05 was considered statistically significant. 
Results: Of 54 patients with neonatal sepsis recruited, the majority had early-onset sepsis (63.0%) and cesarean
section (C-section) delivery (66.7%). A significant association between birth route and neonatal sepsis onset (p=0.046)
was found. However, no significant association was observed between birth route and neonatal sepsis (p=0.321). Term
infants born via C-section were 3.25 times more at risk (95% CI 1.00 – 10.60) of early-onset neonatal sepsis than
infants delivered vaginally. 
Conclusion: C-section delivery can increase the risk of early-onset neonatal sepsis in term infants. 
 

Keywords


  1. Li Z, Karlsson O, Kim R, Subramanian S V. Distribution of under-5 deaths in the neonatal, postneonatal, and childhood periods: a multicountry analysis in 64 low- and middle-income countries. Int J Equity Health. 2021;20(1):1–11.
  2. Primadi O, Ma'ruf A, Hardhana B, Sibuea F, Widiantini W, Indrayani YA, et al. Profil Kesehatan Indonesia 2020. Jakarta: : Kementerian Kesehatan RI. 2021.
  3. Djajakusli S, Harianto A, Etika R, Martono TU. Profil Kematian Neonatus di RSUD dr. Soetomo. Sari Pediatr. 2017;18(6):474.
  4. Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet. 2017;390(10104):1770–80.
  5. Rafi MA, Miah MMZ, Wadood MA, Hossain MG. Risk factors and etiology of neonatal sepsis after hospital delivery: a case-control study in a tertiary care hospital of Rajshahi, Bangladesh. PLoS One. 2020;15(11):1–14.
  6. Mehar V, Agarwal S, Singh R, Agarwal A, Agrawal N, Majethia A. Relationship between gestational age and mode of delivery with neonatal septicemia. Int J Contemp Pediatr. 2016;3(3):891–5.
  7. Madan JC, Farzan SF, Hibberd PL, Karagas MR. Normal neonatal microbiome variation in relation to environmental factors, infection and allergy. Curr Opin Pediatr. 2012;24(6):753–9.
  8. Shaw AG, Sim K, Randell P, Cox MJ, McClure ZE, Li MS, et al. Late-Onset bloodstream infection and perturbed maturation of the gastrointestinal microbiota in premature infants. PLoS One. 2015;10(7):1–14.
  9. Abdellatif M, Al-Khabori M, Rahman A, Khan AA, Al-Farsi A, Ali K. Outcome of late-onset neonatal sepsis at a tertiary hospital in Oman. Oman Med J. 2019;34(4):302–7.
  10. Olivier F, Bertelle V, Shah PS, Drolet C, Piedboeuf B. Association between birth route and late-onset sepsis in very preterm neonates. J Perinatol. 2016;36(12):1083–7.
  11. Siakwa M, Kpikpitse D, Mupepi S, Sylvia C, Semuatu M. Neonatal Sepsis in Rural Ghana: A Case Control Study of Risk Factors in a Birth Cohort. Int J Res Med Heal Sci. 2014;4(5):72–83.
  12. Martua YS. Analisis Faktor – Faktor yang Berhubungan Dengan Kejadian Sepsis Neonatorum di RSUD Taluk Kuantan. J Ilm Kesehat. 2021;13(1):55–63.
  13. World Health Organization. Seventieth World Health Assembly. WHA Resolution A70/13 - Improving the prevention, diagnosis and clinical management of sepsis. Report by the Secretariat. Geneva: World Health Organization. 2017.
  14. Jumah DS, Hassan AK, Mea A. Predictors of Mortality Outcome in Neonatal Sepsis. Med J Basrah Univ. 2007;25(1):11–8.
  15. Zambri H, Fetriyah UH, Nito PJB. The relationship between birth weight and neonatal sepsis incidence: a literature review. Int J Clin Invent Med Sci. 2021;3(2):93–100.
  16. Patel AL, Johnson TJ, Engstrom JL, Fogg LF, Jegier BJ, Bigger HR, et al. Impact of early human milk on sepsis and healthcare costs in very low birth weight infants. J Perinatol. 2013;33(7):514–9.
  17. Onwuanaku CA, Okolo SN, Ige KO, Okpe SE, Toma BO. The effects of birth weight and gender on neonatal mortality in north central Nigeria. BMC Res Notes. 2011;4(1):562.
  18. Chandra R, Federici S, Haskó G, Deitch EA SZ. Female X-chromosome mosaicism for gp91phox expression diversifies leukocyte responses during endotoxemia. Crit Care Med. 2010;38(10):2003–10.
  19. Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, et al. Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants. N Engl J Med. 2002;347(4):240-247.
  20. Shah G, Budhathoki S, Das B, Mandal R. Risk factors in early neonatal sepsis. Kathmandu Univ Med. 2006;4:187–91.
  21. Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646
  22. Stoll BJ, Hansen NI, Sánchez PJ, Faix RG, Poindexter BB, Van Meurs KP, et al. Early onset neonatal sepsis: The burden of group B streptococcal and E. coli disease continues. Pediatrics. 2011;127(5):817–26.
  23. Yahya FB, Hathcock MA. A Retrospective review of neonatal sepsis among GBS-colonized Women undergoing planned cesarean section after labor onset or rupture of membranes. Infect Dis Obstet Gynecol. 2020;2020:4365259.
  24. Noah FN, Doya LJ, Jouni O. Perinatal Risk factors and early onset of neonatal sepsis. Int J Pediatr Res. 2022;8:088.
  25. Hornik CP, Fort P, Clark RH, Watt K, Benjamin DK, Smith PB, et al. Early and late-onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum Dev. 2012;88(2): 69-74.
  26. Dessole S, Cosmi E, Balata A, Uras L, Caserta D, Capobianco G, et al. Accidental fetal lacerations during cesarean delivery: experience in an Italian teritiary university hospital. Am J Obstet Gynecol . 2004;191(5):1673–7.
  27. Adatara P, Afaya A, Salia SM, et al. Risk factors for neonatal sepsis: a retrospective case-control study among neonates who were delivered by caesarean section at the trauma and specialist hospital, Winneba, Ghana. Biomed Res Int. 2018;
    2018:6153501.
  28. Hook B, Kiwi R, Amini SB, Fanaroff A, Hack M. Neonatal morbidity after elective repeat cesarean section and trial of labor. Pediatrics. 1997;100:348–353.
  29. Weston EJ, Pondo T, Lewis MM, Martell-Cleary P, Morin C, Jewell B, et al. The burden of invasive early-onset neonatal sepsis in the United States, 2005–2008. Pediatr Infect Dis J. 2011;30:937–41.
  30. Tapiainen T, Koivusaari P, Brinkac L, Lorenzi HA, Salo J, Renko M, et al. Impact of intrapartum and postnatal antibiotics on the gut microbiome and emergence of antimicrobial resistance in infants. Sci Rep. 2019;9(1):10635.
  31. Grölund M-M, Lehtonen O-P, Eerola E, Kero P. Fecal Microflora in Healthy Infants Born by Different Methods of Delivery: Permanent Changes in intestinal flora after cesarean delivery. J Pediatr Gastroenterol Nutr. 1999;28(1): 19–25.
  32. Betrán AP, Ye J, Moller AB, Zhang J, Gülmezoglu AM, Torloni MR. The increasing trend in cesarean section rates: Global, regional and national estimates: 1990-2014. PLoS One. 2016;11(2): e0148343.
  33. Cegolon L, Mastrangelo G, Campbell OM, Giangreco M, Alberico S, Monasta L, et al. Correction: Length of stay following cesarean sections: A population-based study in the Friuli Venezia Giulia region (North-Eastern Italy), 2005-2015. PLoS One. 2019;14(2):e0210753.
  34. Alkali B, Agwu E, Sarkinfada F, Idris AM, Mada SB. C Association of nosocomial infection with a prolonged hospital stay in Kano Nigeria. Bayero J Pure Appl Sci. 2019;12(2):149–55.
  35. Kawagoe JY, Segre CAM, Pereira CR, Cardoso MFS, Silva CV, Fukushima JT. Risk factors for nosocomial infections in critically ill newborns: a 5-year prospective cohort study. Am J Infect Control. 2001;29(2):109–14.
  36. Bhatta DR, Subramanya SH, Hamal D, Shrestha R, Gauchan E, Basnet S, et al. Bacterial contamination of neonatal intensive care units: how safe are the neonates?. Antimicrob Resist Infect Control. 2021;10(1):26.