DOI: http://dx.doi.org/10.18203/2349-3291.ijcp20193711

Role of serum procalcitonin as a marker for diagnosing neonatal sepsis

Haniya Jafar, Jyotsna Agarwal, Raj Kumar Kalyan, Shruti Radera, Sheetal Verma, Mala Kumar, Shalini Tripathi

Abstract


Background: Neonatal sepsis is a continuing problem causing significant burden on health care, especially in developing world. As blood culture has low sensitivity in diagnosis of neonatal sepsis, strong clinical suspicion along with combination of different laboratory tests is required. The data available for extensively studied acute phase reactant, procalcitonin (PCT) remains controversial. This study was done to assess role of PCT alone and in combination with different tests for diagnosing neonatal sepsis.

Methods: Blood samples of 275 neonates (>35 weeks of gestation) admitted to NICU, with suspicion of neonatal sepsis were collected for bacterial culture, serum procalcitonin level and sepsis screen (CRP, mESR, I/T ratio, Total Leucocyte Count, Absolute Neutrophil Count).

Results: Blood culture was positive in 30.5% of enrolled neonates. At a cut-off value of 0.5 ng/ml the sensitivity, specificity, PPV, NPV of serum PCT in neonatal sepsis cases was 73.8%, 47.1%, 48%, 80.4% respectively. Serum PCT was found raised in 60 (48.8%) clinically suspected cases of neonatal sepsis where sepsis screen and blood culture both were negative, also it was not raised in 17 (32.7%) of clinically suspected cases of septicemia where both blood culture and sepsis screen were positive. Amongst other individual tests, CRP was found to have best sensitivity (79.7%) and NPV (85%) followed by PCT (73.8% and 80.4%) while best specificity was found for I/T ratio (93.7%) followed by mESR (89%) for diagnosis of neonatal sepsis with positive blood culture. Best NPV was seen for combination of PCT+CRP+I/T ratio (95.6%) for the suspected cases of neonatal sepsis.

Conclusions: Thus, we conclude that serum PCT can play a useful role when combined with other test markers but may not find its way as a sole diagnostic marker for diagnosing neonatal sepsis in term/near term babies.


Keywords


Blood culture, C reactive protein, Neonatal sepsis, Procalcitonin

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References


Network NN. National Neonatal-Perinatal Database (Report 2002-2003). InNational Neonatology Forum NNPD Network, New Delhi, India 2005. Available at: http://www.newbornwhocc.org/pdf/nnpd_report_2002-03.PDF. Accessed 9 May 2018.

Liu L, Oza S, Hogan D, Chu Y, Perin J, Zhu J, Lawn JE, Cousens S, Mathers C, Black RE. Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals. The Lancet. 2016;388(10063):3027-35.

Cloherty JP, Eichenwald EC, Hansen AR, Stark AR. Manual of Neonatal Care. 7th ed. Philadelphia: Lippincott Williams and Wilkins; 2012;624-655.

Bhandari V. Effective biomarkers for diagnosis of neonatal sepsis. J Pediatr Infect Dis Soc. 2014;3(3):234-45.

Meem M, Modak JK, Mortuza R, Morshed M, Islam MS, Saha SK. Biomarkers for diagnosis of neonatal infections: A systematic analysis of their potential as a point-of-care diagnostics. J Global Health. 2011;1(2):201.

Agarwal R, Deorari A, Paul VK. AIIMS Protocol in Neonatology. New Delhi: CBS; Chapter 12, Neonatal Sepsis. 2015;163-173.

Dong Y, Speer CP. Late-onset neonatal sepsis: recent developments. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2015;100(3):F257-63.

Jeergal NA, Rizwan-u-zama NA, Malagi N, Farooqui F, Ukkali SB, Naganoor R, Thobbi AN. Procalcitonin as a marker of neonatal sepsis. Al Ameen J Med Sci. 2016;9(1):70-3.

Vasantha AR, Kutty SN, Theodore RB. Neonatal sepsis: Aetiological agents and risk factors. Journal of The Academy of Clinical Microbiologists. 2017;19(1):36.

Lapillonne A, Basson E, Monneret G, Bienvenu J, Salle BL. Lack of specificity of procalcitonin for sepsis diagnosis in premature infants. The Lancet. 1998;351(9110):1211-2.

Monneret G, Labaune JM, Isaac C, Bienvenu F, Putet G, Bienvenu J. Procalcitonin and C‐reactive protein levels in neonatal infections. Acta Paediatr. 1997;86(2):209-12.

Chiesa C, Natale F, Pascone R, Osborn JF, Pacifico L, Bonci E, De Curtis M. C reactive protein and procalcitonin: reference intervals for preterm and term newborns during the early neonatal period. Clinica Chimica Acta. 2011;412(11-12):1053-9.

Chiesa C, Panero A, Rossi N, Stegagno M, Giusti MD, Osborn JF, Pacifico L. Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates. Clinic infect dis. 1998;26(3):664-72.

Gebremedhin D, Berhe H, Gebrekirstos K. Risk factors for neonatal sepsis in public hospitals of Mekelle City, North Ethiopia, 2015: unmatched case control study. PloS one. 2016;11(5):e0154798.

Hasan F, Khan SA, Maharoof MK, Muhammed N. Role of procalcitonin in early diagnosis of neonatal sepsis. Int J Contemp Pediatr. 2017;4(2):383-9.

Roy I, Jain A, Kumar M, Agarwal SK. Bacteriology of neonatal septicaemia in a tertiary care hospital of northern India. Ind J Med Microbiol. 2002;20(3):156.

Shah AJ, Mulla SA, Revdiwala SB. Neonatal sepsis: high antibiotic resistance of the bacterial pathogens in a neonatal intensive care unit of a tertiary care hospital. J clinic neonatol. 2012;1(2):72.

Stocker M, Hop WC, van Rossum AM. Neonatal Procalcitonin Intervention Study (NeoPInS): Effect of Procalcitonin-guided decision making on duration of antibiotic therapy in suspected neonatal early-onset sepsis: A multi-centre randomized superiority and non-inferiority Intervention Study. BMC pediatr. 2010;10(1):89.

Ng PC. Diagnostic markers of infection in neonates. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2004;89(3):F229-35.

Polin RA. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatr. 2012;129(5):1006-15.

Hornik CP, Benjamin DK, Becker KC, Benjamin Jr DK, Li J, Clark RH, Cohen-Wolkowiez M, Smith PB. Use of the complete blood cell count in late-onset neonatal sepsis. The Pediatric infectious disease J. 2012;31(8):803.

Newman TB, Puopolo KM, Wi S, Draper D, Escobar GJ. Interpreting complete blood counts soon after birth in newborns at risk for sepsis. Pediatr. 2010;126(5):903-9.

Shah BA, Padbury JF. Neonatal sepsis: an old problem with new insights. Virulence. 2014;5(1):170-8.

Zaka-ur-Rab Z, Kar M, Gupta V, et al. Evaluation of laboratory markers of sepsis screen in the diagnosis of early onset neonatal septicemia. Int J Contemp Pediatr. 2016;3(4):1144-9.

Buch AC, Srivastava V, Kumar H, Jadhav PS. Evaluation of haematological profile in early diagnosis of clinically suspected cases of neonatal sepsis. International Journal of Basic and Applied Med Sci. 2011;1(1):1-6.

Mondal SK, Nag DR, Bandyopadhyay R, Chakraborty D, Sinha SK. Neonatal sepsis: role of a battery of immunohematological tests in early diagnosis. International J Applied Basic Med Res. 2012;2(1):43.

Vinay BS, Girish GN, Adhikari S, et al. Evaluation of septic screen as a diagnostic tool for neonatal sepsis in a tertiary hospital at Mysore. Sch J App Med Sci. 2015;3(2G):1005-1010.

Sharma A, Kutty CV, Sabharwal U, Rathi SU, Mohan H. Diagnostic and prognostic role of CRP and m-ESR in neonatal septicemia. Ind pediatr. 1993;30(3):347-50.

Nargis W, Ibrahim MD, Ahamed BU. Procalcitonin versus C-reactive protein: Usefulness as biomarker of sepsis in ICU patient. International J critic illness injury sci. 2014;4(3):195.

Sakha K, Husseini MB, Seyyedsadri N. The role of the procalcitonin in diagnosis of neonatal sepsis and correlation between procalcitonin and C-reactive protein in these patients. Pak J Bio Sci. 2008;11(14):1785.

Wagner TA, Gravett CA, Healy S, Soma V, Patterson JC, Gravett MG, Rubens CE. Emerging biomarkers for the diagnosis of severe neonatal infections applicable to low resource settings. J global health. 2011;1(2):210.

Blommendahl J, Janas M, Laine S, Miettinen A, Ashorn P. Comparison of procalcitonin with CRP and differential white blood cell count for diagnosis of culture-proven neonatal sepsis. Scandinavian J infect dis. 2002;34(8):620-2.

Wang H, Yin F, Shen DX, Zhang YJ, Luo YP, Liu CJ, Wang KF, Zhou G, Ye LY, Chen G, Wang XN. Predictive value of procalcitonin for excluding bloodstream infection: results of a retrospective study and utility of a rapid, quantitative test for procalcitonin. J International Med Res. 2013;41(5):1671-81.

Abdollahi A, Shoar S, Nayyeri F, Shariat M. Diagnostic value of simultaneous measurement of procalcitonin, interleukin-6 and hs-CRP in prediction of early-onset neonatal sepsis. Mediterranean J hematol infect dis. 2012;4(1).

Altunhan H, Annagür A, Örs R, Mehmetoğlu I. Procalcitonin measurement at 24 hours of age may be helpful in the prompt diagnosis of early-onset neonatal sepsis. International J Infect Dis. 2011;15(12):e854-8.

Misra RN, Jadhav SV, Ghosh P, Gandham N, Angadi K, Vyawahare C. Role of sepsis screen in the diagnosis of neonatal sepsis. Med J Dr. DY Patil Uni. 2013;6(3):254.