Skip to main content

Advertisement

Log in

Cerebral blood flow velocity in early-onset neonatal sepsis and its clinical significance

European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Chorioamnionitis is a known risk factor for neurological damage in newborns. The present study aimed at assessing the changes in cerebral blood flow velocity (CBFV) in early-onset neonatal sepsis (EONS) and determining its predictive value as well as prognostic significance. Inborn neonates with antenatal risk factors for chorioamnionitis were followed up for development of EONS, diagnosed by presence of clinical signs along with positive blood culture and/or elevated interleukin-6 (IL-6) concentrations (≥50 pg/mL) in umbilical cord blood. Comparison group was formed by asymptomatic neonates who had risk factors for chorioamnionitis but did not develop EONS and cord blood IL-6 concentrations were <50 pg/mL. CBFV (resistance and pulsatility indices, peak systolic flow velocity, and vascular diameter) of internal carotid, vertebral, and middle cerebral arteries was assessed by transcranial Doppler ultrasonography within 24 h of birth. The babies were kept under clinical and radiological follow-up for a minimum period of 6 months. Data were analyzed by SPSS 16.0. Final study group contained 55 neonates with sepsis and 35 asymptomatic control neonates. Blood culture was positive in 27 babies of the sepsis group with a preponderance of Gram-negative bacterial isolation. Significantly lower resistance, vasodilatation, and higher blood flow were noted in all the cerebral arteries of the sepsis group. Increase in CBFV was correlated with elevated IL-6 concentrations. CBFV parameters showed significant predictive accuracy as early diagnostic markers of EONS. Among the sepsis group, 14 patients showed signs of intracranial hemorrhage during the hospital stay of which four expired and six showed signs of ventricular dilatation during follow-up. These patients had significantly higher CBFV compared to those who survived. Assessment of CBFV at early hours of birth can be adopted as an additional bedside, non-invasive investigation with immediate diagnostic and late prognostic significance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Alexander JM, Gilstrap LC, Cox SM, McIntire DM, Leveno KJ (1998) Clinical chorioamnionitis and the prognosis for very low birth weight infants. Obstet Gynecol 91:725–729

    Article  PubMed  CAS  Google Scholar 

  2. Altman DI, Perlman JM, Volpe JJ, Powers WJ (1993) Cerebral oxygen metabolism in newborns. Pediatrics 92:99–104

    PubMed  CAS  Google Scholar 

  3. Arad I, Bar-Oz B, Ergaz Z, Nir A, Barak V (2010) Interleukin-6 and N-terminal pro-brain natriuretic peptide cord blood levels in premature infants: correlations with perinatal variables. Isr Med Assoc J 12:419–423

    PubMed  Google Scholar 

  4. Bhat YR, Lewis LE, Ke V (2011) Bacterial isolates of early-onset neonatal sepsis and their antibiotic susceptibility pattern between 1998 and 2004: an audit from a center in India. Ital J Pediatr 37:32

    Article  Google Scholar 

  5. Duncombe G, Veldhuizen RA, Gratton RJ, Han VK, Richardson BS (2010) IL-6 and TNFalpha across the umbilical circulation in term pregnancies: relationship with labour events. Early Hum Dev 86:113–117

    Article  PubMed  CAS  Google Scholar 

  6. Furukawa S, Sameshima H, Ikenoue T (2008) Circulatory disturbances during the first postnatal 24 hours in extremely premature infants 25 weeks or less of gestation with histological fetal inflammation. J Obstet Gynaecol Res 34:27–33

    PubMed  Google Scholar 

  7. Greisen G (2005) Autoregulation of cerebral blood flow in newborn babies. Early Hum Dev 81:423–428

    Article  PubMed  Google Scholar 

  8. Jayasinghe D, Gill AB, Levene MI (2003) CBF reactivity in hypotensive and normotensive preterm infants. Pediatr Res 54:848–853

    Article  PubMed  Google Scholar 

  9. Kuster H, Weiss M, Willeitner AE, Detlefsen S, Jeremias I, Zbojan J, Geiger R, Lipowsky G, Simbruner G (1998) Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. Lancet 352:1271–1277

    Article  PubMed  CAS  Google Scholar 

  10. Lawn JE, Cousens S, Zupan J (2005) 4 million neonatal deaths: when? Where? Why? Lancet 365:891–900

    Article  PubMed  Google Scholar 

  11. Leviton A, Dammann O (2004) Coagulation, inflammation, and the risk of neonatal white matter damage. Pediatr Res 55:541–545

    Article  PubMed  Google Scholar 

  12. MacKenzie ET, McCulloch J, O’Keane M, Pickard JD, Harper AM (1976) Cerebral circulation and norepinephrine: relevance of the blood–brain barrier. Am J Physiol 231:483–488

    PubMed  CAS  Google Scholar 

  13. Maekawa T, Fuji Y, Sadamitsu D (1981) Cerebral circulation and metabolism in patients with septic encephalopathy. Am J Emerg Med 9:139–145

    Article  Google Scholar 

  14. Martin H, Olander B, Norman M (2001) Reactive hyperemia and interleukin 6, interleukin 8, and tumor necrosis factor-α in the diagnosis of early-onset neonatal sepsis. Pediatrics 108:1–6

    Article  Google Scholar 

  15. Martínez Nadal S, Elizari Saco MJ, Fernández Delclos D, Demestre Guasch X, Sala Castellví P, Vila Ceren C, Raspall Torrent F (2008) Cord blood levels of interleukin 6 in preterm infants as an early marker of neonatal morbidity. An Pediatr (Barc) 68:218–223

    Article  Google Scholar 

  16. Matta BF, Stow PJ (1996) Sepsis-induced vasoparalysis does not involve the cerebral vasculature: indirect evidence from autoregulation and carbon dioxide reactivity studies. Br J Anaesth 76:790–794

    Article  PubMed  CAS  Google Scholar 

  17. Pacora P, Chaiworapongsa T, Maymon E, Kim YM, Gomez R, Yoon BH, Ghezzi F, Berry SM, Qureshi F, Jacques SM, Kim JC, Kadar N, Romero R (2002) Funisitis and chorionio vasculitis: the histologic counterpart of the fetal inflammatory response syndrome. J Matern Fetal Neonatal Med 11:18–25

    Article  PubMed  CAS  Google Scholar 

  18. Pezzati M, Dani C, Biadaioli R, Filippi L, Biagiotti R, Giani T, Rubaltelli FF (2002) Early postnatal Doppler assessment of cerebral blood flow velocity in healthy preterm and term infants. Dev Med Child Neurol 44:745–752

    Article  PubMed  Google Scholar 

  19. Pfister D, Schmidt B, Smielewski P, Siegemund M, Strebel SP, Rüegg S, Fülesdi B (2008) Intracranial pressure in patients with sepsis. Acta Neurochir Suppl 102:71–75

    Article  PubMed  CAS  Google Scholar 

  20. Rocha G, Proença E, Quintas C, Rodrigues T, Guimaraes H (2007) Chorioamnionitis and brain damage in the preterm newborn. J Matern Fetal Neonatal Med 20:745–749

    Article  PubMed  Google Scholar 

  21. Rosengarten B, Wolff S, Klatt S, Schermuly RT (2009) Effects of inducible nitric oxide synthase inhibition or norepinephrine on the neurovascular coupling in an endotoxic rat shock model. Crit Care 13:R139

    Article  PubMed  Google Scholar 

  22. Semmler A, Hermann S, Mormann F (2008) Sepsis causes neuroinflammation and concomitant decrease of cerebral metabolism. J Neuroinflam 5:38

    Article  Google Scholar 

  23. Skrablin S, Lovric H, Banovic V, Kralik S, Dijakovic A, Kalafatic D (2007) Maternal plasma interleukin-6, interleukin-1beta and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery. J Matern Fetal Neonatal Med 20:335–341

    Article  PubMed  CAS  Google Scholar 

  24. Smulian JC, Vintzileos AM, Lai YL (1999) Maternal chorioamnionitis and umbilical vein interleukin-6 levels for identifying early neonatal sepsis. J Matern Fetal Med 8:88–94

    Article  PubMed  CAS  Google Scholar 

  25. Szatmairi S, Vacgh T, Csomas A, Hallay J, Takaics I, Molnair C, Fulesdi B (2010) Impaired cerebrovascular reactivity in sepsis-associated encephalopathy studied by acetazolamide test. Crit Care 14:R50

    Article  Google Scholar 

  26. Terborg C, Schummer W, Albrecht M (2001) Dysfunction of vasomotor reactivity in severe sepsis and septic shock. Intensive Care Med 27:1231–1234

    Article  PubMed  CAS  Google Scholar 

  27. Toti P, De Felice C, Occhini R, Schuerfeld K, Stumpo M, Epistolato MC, Vatti R, Buonocore G (2004) Spleen depletion in neonatal sepsis and chorioamnionitis. Am J Clin Pathol 122:765–771

    Article  PubMed  Google Scholar 

  28. Tsering DC, Chanchal L, Pal R, Kar S (2011) Bacteriological profile of septicemia and the risk factors in neonates and infants in Sikkim. J Glob Infect Dis 3:42–45

    Article  PubMed  Google Scholar 

  29. Vasiljevia B, Gojnia M, Maglajlia-Djukia S, Antonovia O (2010) Normal values of cerebral blood flow velocities in neonates. Srp Arh Celok Lek 138:186–191

    Article  Google Scholar 

  30. Vincent JL (2001) Microvascular endothelial dysfunction: a renewed appreciation of sepsis pathophysiology. Crit Care 5:S1–S5

    Article  PubMed  CAS  Google Scholar 

  31. Volpe JJ (1998) Brain injury in the premature infant: overview of clinical aspects, neuropathology, and pathogenesis. Semin Pediatr Neurol 5:135–351

    Article  PubMed  CAS  Google Scholar 

  32. Volpe JJ (2001) Intracranial hemorrhage: germinal–intraventricular hemorrhage of the preterm infant. Neurology of the newborn. Saunders, Philadelphia, pp 428–496

    Google Scholar 

  33. Wilson JX, Young GB (2003) Sepsis-associated encephalopathy: evolving concepts. Can J Neurol Sci 30:98–105

    PubMed  Google Scholar 

  34. Yanowitz TD, Jordan JA, Gilmour CH, Towbin R, Bowen A, Roberts JM, Brozanski BS (2002) Hemodynamic disturbances in premature infants born after chorioamnionitis: association with cord blood cytokine concentrations. Pediatr Res 51:310–316

    Article  PubMed  Google Scholar 

  35. Yoon BH, Romero R, Park JS, Kim M, Oh S, Kim CJ, Jun JK (2000) The relationship among inflammatory lesions of the umbilical cord (funisitis), umbilical cord plasma interleukin 6 concentration, amniotic fluid infection, and neonatal sepsis. Am J Obstet Gynecol 183:1124–1129

    Article  PubMed  CAS  Google Scholar 

  36. Zakariya BP, Bhat V, Harish BN, Arun Babu T, Joseph NM (2011) Neonatal sepsis in a tertiary care hospital in South India: bacteriological profile and antibiotic sensitivity pattern. Indian J Pediatr 78:413–417

    Article  PubMed  Google Scholar 

  37. Zwibel WJ, Pellerito JS (2005) Basic concepts of Doppler frequency spectrum analysis and ultrasound blood flow imaging. In: Zwibel WJ, Pellerito JS (eds) Introduction to vascular ultrasonography, 5th edn. Elsevier Saunders, Philadelphia, pp 61–89

    Chapter  Google Scholar 

Download references

Conflict of interest statement

All the authors declare that this research has not been funded or sponsored by any organization. None of the authors has any financial relationship with any organization and there is no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sriparna Basu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Basu, S., Dewangan, S., Shukla, R.C. et al. Cerebral blood flow velocity in early-onset neonatal sepsis and its clinical significance. Eur J Pediatr 171, 901–909 (2012). https://doi.org/10.1007/s00431-011-1643-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-011-1643-y

Keywords

Navigation