Umbilical cord blood interleukin-6 level as a predictor of early-onset neonatal sepsis

  • Arya Adnan Fadilah Department of Child Health, Faculty of Medicine, Public Health, and Nursing Dr. Sardjito Hospital
  • Ekawaty Lutfia Haksari Department of Child Health, Faculty of Medicine, Public Health, and Nursing Dr. Sardjito Hospital
  • Setya Wandita Department of Child Health, Faculty of Medicine, Public Health, and Nursing Dr. Sardjito Hospital
Keywords: : neonatal sepsis; IL-6; clinical sepsis


Background Neonatal sepsis is a global health problem contributing significantly to neonatal morbidity and mortality. It is difficult to clinically distinguish neonates with and without sepsis. Interleukin-6 (IL-6) concentration in neonates has high sensitivity and specificity to predict neonatal sepsis in infants at risk.

Objective  To determine the utility of umbilical cord blood IL-6 as a predictor of early-onset neonatal sepsis.

Methods This prospective cohort study was conducted in neonates born to mothers with sepsis risk factors from December 2020 to January 2021. We measured IL-6 from umbilical cord blood taken after placental expulsion. IL-6 ³16.4 pg/ml was considered to be elevated. Subjects were monitored for signs of clinical sepsis until 72 hours after birth. We also recorded the presence of other maternal and infant risk factors of sepsis and assessed association between IL-6 and other risk factors with the occurrence of sepsis, expressed as relative risk (RR) with 95% confidence interval (95%CI).

Results During the study period, 40 neonates were born to mothers with sepsis risk factors; 13 (32.5%) developed clinical sepsis. Significantly more infants with elevated IL-6 developed neonatal sepsis (55.5%) than those with normal IL-6 (13.6%). After multivariate analysis incorporating other significant variables, the risk factors predictive of clinical early-onset neonatal sepsis were IL-6 [RR 5.54 (95%CI 1.68-18.25); P=0.016], prematurity [RR 4.92 (95%CI 1.66-14.59); P=0.014], and initial Apgar score [RR 3.38 (95%CI 1.34-3.38); P=0.046].

Conclusion In neonates with maternal risk factors, an IL-6 level of ³16.4 pg/ml is associated with an increased risk of early-onset neonatal sepsis.


1. UNICEF. Maternal and newborn health disparities country profiles - Indonesia. [cited 2020 Apr 8]. Available from:
2. Oza S, Lawn JE, Hogan DR, Mathers C, Cousens SN. Neonatal cause-of-death estimates for the early and late neonatal periods for 194 countries: 2000–2013. Bull World Health Org. 2015;93:19-28. DOI:
3. Hammad E, Zainab MS. Meta-analysis on factors influencing early onset neonatal sepsis. Sch J Appl Sci Res. 2018;1:20-22
4. Esaiassen E, Fjalstad JW, Juvet LK, van den Anker JN, Klingenberg C. Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis. J Antimicrob Chemother. 2017;72:1858–70. DOI:
5. Polin RA, Committee on Fetus and Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2012;129:1006–15. DOI:
6. Stoll BJ, Hansen NI, Adams-Chapman I, Fanaroff AA, Hintz SR, Vohr B, et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA. 2004;292:2357–65. DOI:
7. Chu S, Hsu JF, Lee CW, Lien R, Huang HR, Chiang MC, et al. Neurological complications after neonatal bacteremia: the clinical characteristics, risk factors, and outcomes. PLoS One. 2014;9:e105294. DOI:
8. Camacho-Gonzales A, Spearman PW, Stoll BJ. Neonatal infectious disease: evaluation of neonatal sepsis. Pediatr Clin North Am. 2013;60:367–89. DOI:
9. Cernada M, Badia N, Modesto V, Alonso R, Mejias A, Golombek S, et al. Cord blood interleukin-6 as a predictor of early-onset neonatal sepsis. Acta Paediatr. 2012;101:203–7. DOI:
10. Khan A, Ali Z. Normal ranges for acute phase reactants (interleukin-6, tumour necrosis factor-alpha and C-reactive protein) in umbilical cord blood of healthy term neonates at the Mount Hope Women’s Hospital, Trinidad. West Indian Med J. 2014;63:465-9. DOI:
11. Sonawane VB, Mehkarkar NS, Jadhav PB, Gaikwad SU, Kadam NN. Study of interleukin-6 levels in early diagnosis of neonatal sepsis. Int J Res Med Sci. 2015;3:41-6. DOI:
12. Eri? Ž, Konjevi? S. Proinflammatory cytokines in a newborn: a literature review. Signa Vitae. 2017;13:10-3.
13. Prashant A, Vishwanath P, Kulkarni P, Narayana PS, Gowdara V, Nataraj SM, et al. Comparative assessment of cytokines and other inflammatory markers for the early diagnosis of neonatal sepsis-a case control study. PLoS One. 2013;8:e68426. DOI:
14. Schultz C, Rott C, Temming P, Schlenke P, Moller JC, Bucsky P. Enhanced interleukin-6 and interleukin-8 synthesis in term and preterm infants. Pediatr Res. 2002;51:317-22. DOI:
15. Klingenberg C, Kornelisse RF, Buonocore G, Maier RF, Stocker M. Culture-negative early-onset neonatal sepsis - at the crossroad between efficient sepsis care and antimicrobial stewardship. Front Pediatr. 2018;6:285. DOI:
16. Fjalstad JW, Stensvold HJ, Bergseng H, Simonsen GS, Salvesen B, Ronnestad AE, et al. Early-onset sepsis and antibiotic exposure in term infants. Pediatr Infect Dis J. 2016;35:1-6. DOI:
17. Kenis G, Teunissen C, Jongh R De, Bosmans E, Steinbusch H, et al. Stability of interleukin 6 , soluble interleukin 6 receptor, interleukin 10 and CC16 in human serum. Cytokine. 2002;19:228-35. DOI:
18. 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. DOI:
19. Chan GJ, Lee AC, Baqui AH, Tan J, Black RE. Risk of early-onset neonatal infection with maternal infection or colonization: a global systematic review and meta-analysis. PLoS Med. 2013;10:e1001502. DOI:
20. Reed BD, Schibler KR, Deshmukh H, Ambalavanan N, Morrow AL. The impact of maternal antibiotics on neonatal disease. J Pediatr. 2018;197:97-103. DOI:
21. Adatara P, Afaya A, Salia SM, Afaya RA, Kuug AK, Agbinku E, 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. DOI:
22. Dessole S, Cosmi E, Balata A, Uras L, Caserta D, Capobianco G, et al. Accidental fetal lacerations during cesarean delivery: experience in an Italian level III university hospital. Am J Obstet Gynecol. 2004;191;1673–7. DOI:
23. Døllner H, Vatten L, Linnebo I, Zanussi GF, Laerdal A, Austgulen R. Inflammatory mediators in umbilical plasma from neonates who develop early-onset sepsis. Biol Neonate. 2001;80:41–7. DOI:
How to Cite
Fadilah A, Haksari E, Wandita S. Umbilical cord blood interleukin-6 level as a predictor of early-onset neonatal sepsis. PI [Internet]. 28Oct.2022 [cited 28May2024];62(5):304-. Available from:
Received 2021-06-16
Accepted 2022-10-28
Published 2022-10-28