|Year : 2019 | Volume
| Issue : 3 | Page : 183-189
Prognostic value of red cell distribution width, platelet parameters, and the hematological scoring system in neonatal sepsis
Suzan O Mousa MD , Asmaa N Moustafa, Hend M Aly
Department of Pediatrics, Clinical Pathology, Minia University Hospital, El-Minya, Egypt
|Date of Submission||19-Mar-2019|
|Date of Acceptance||24-Apr-2019|
|Date of Web Publication||05-Dec-2019|
Suzan O Mousa
Department of Pediatric, Minia University Hospital, El-Minya, 61111
Source of Support: None, Conflict of Interest: None
Purpose Neonatal sepsis has wide variations of clinical presentations, which may not reflect the severity of the disease. Our objective was to investigate the prognostic value of the hematological scoring system (HSS), red cell distribution width (RDW), mean platelet volume (MPV), and platelet distribution width (PDW) in neonatal sepsis at the time of admission to the neonatal ICU.
Patients and methods The study included two groups: the neonatal sepsis group which included 64 neonates with neonatal sepsis and the control group which included 60 neonates with sex, gestational, and postnatal ages matched with the previous group. RDW, MPV, and PDW were measured for all included neonates. Score for Neonatal Acute Physiology-II score and HSS were determined for the sepsis group within 12 h of admission to the neonatal ICU.
Results RDW, MPV, and PDW were significantly higher in the sepsis group than the control group (P<0.0001). RDW, MPV, PDW, and HSS were not significantly different between neonates with culture-proven sepsis and those with probable sepsis (P>0.05). But on comparing their levels in survivors with the nonsurvivors, all of them were significantly higher in the nonsurvivors (P<0.05), except for HSS (P=0.4). RDW was the most sensitive hematological marker studied to predict mortality, as RDW and Score for Neonatal Acute Physiology-II score more than or equal to 40 had the same sensitivity of 77.8%, followed by MPV (61.1%), and then PDW (50%). Meanwhile, the MPV was the most specific (88.1%). Receiver operating characteristic curve analysis for HSS was not of statistical significance (P>0.05).
Conclusion RDW is the most sensitive hematological marker to predict mortality in neonatal sepsis, followed by MPV and PDW. HSS is still a diagnostic rather than a prognostic score.
Keywords: mean platelet volume, neonatal sepsis syndrome, platelet distribution width, red cell distribution width
|How to cite this article:|
Mousa SO, Moustafa AN, Aly HM. Prognostic value of red cell distribution width, platelet parameters, and the hematological scoring system in neonatal sepsis. Egypt J Haematol 2019;44:183-9
|How to cite this URL:|
Mousa SO, Moustafa AN, Aly HM. Prognostic value of red cell distribution width, platelet parameters, and the hematological scoring system in neonatal sepsis. Egypt J Haematol [serial online] 2019 [cited 2020 Dec 3];44:183-9. Available from: http://www.ehj.eg.net/text.asp?2019/44/3/183/272367
| Introduction|| |
Neonatal sepsis remains one of the leading causes of morbidity and mortality among both term and preterm infants especially in the developing countries . While some reports from developed countries demonstrated that the incidence of neonatal sepsis varies from 1 to 5 cases per 1000 live births, some other population-based studies from developing countries have reported clinical sepsis rates ranging from 49 to 170 per 1000 live births .
In the 1990s, Richardson et al.  developed the Score for Neonatal Acute Physiology (SNAP), followed by a simplified version of the score, using only five variables to be measured within 12 h of admission (SNAP-II) and its perinatal extension (SNAPPE-II). These scoring systems have been validated in studies with large numbers of patients and have been shown to be good predictors of mortality in newborns in neonatal intensive care units (NICU). The use of scoring systems has also allowed comparison of mortality rates from NICUs of different perinatal hospitals adjusted by severity of the disease at admission .
Numerous studies had found red cell distribution width (RDW) and platelet morphology to vary significantly in pathological conditions associated with inflammation and infection ,,,,. Several studies have reported that RDW shows the predictive value of all-cause mortality in critically ill or ICU patients .
Also, platelet parameters such as mean platelet volume (MPV) and platelet distribution width (PDW)  have been routinely available to the clinicians for some time. However, their significance in various platelet disorders has only been studied recently .
The hematological scoring system (HSS) is used to improve the efficiency of the complete blood count (CBC) as a screening test for sepsis. It is a simple, quick, cost-effective, and readily available tool with high sensitivity and specificity in the early diagnosis of neonatal sepsis . But no study had ever addressed its prognostic value.
In this study, we aimed to investigate the prognostic value of HSS, RDW, MPV, and PDW in neonatal sepsis at the time of admission to the NICU. As these markers are available as parts of any routine CBC, we compared them with the clinical outcome and SNAP-II score.
| Patients and methods|| |
This prospective case–control study was carried out in the NICU, Minia University Children Hospital, during the period from January 2016 to June 2016. All full-term neonates admitted to the NICU with neonatal sepsis during this period were included in our study as the neonatal sepsis group. This group included 64 neonates.
The criteria for inclusion of neonates into the neonatal sepsis group were neonates presented with either proven sepsis (clinical signs of sepsis with the isolation of the pathogen from blood, CSF, or urine) or probable sepsis. Probable sepsis was diagnosed when clinical signs of sepsis were evident without isolated pathogen, with one or more of the following criteria: (a) predisposing factors such as maternal fever, foul smelling liquor, or prolonged rupture of membrane more than 12 h, gastric polymorph count of more than 6/HPF, (b) positive sepsis screen with two of the following four parameters: total leukocyte count less than 5000/mm3, band cell to total neutrophil ratio of more than or equal to 0.2, C-reactive protein (CRP) more than or equal to 0.6 mg/dl, micro-ESR more than or equal to 15 mm at the end of the first hour, and (c) radiological evidence of pneumonia.
We excluded from our study premature neonates and neonates with congenital heart diseases, congenital anomalies, hypoxic ischemic encephalopathy, hyaline membrane disease, and prior antibiotic exposure.
Another 60 apparently healthy neonates, sex, gestational, and postnatal ages matched with the neonatal sepsis group, were enrolled as the control group. They were randomly selected from the neonates admitted with their mothers in the obstetric department or visiting the neonatal outpatient clinic for follow-up.
The study was explained in detail to the parents or legal guardians of the participant neonates and written consents were taken from them. The study was designed respecting the expected ethical aspects. It was performed according to the Declaration of Helsinki 1975, as revised in 2008 and approved by the Institutional Review Board and Medical Ethics Committee of Minia University Hospital.
All enrolled neonates in the neonatal sepsis group had their illness severity assessed using SNAP-II. This score consists of six physiological parameters, namely the lowest mean arterial pressure, worst ratio of partial pressure of oxygen to a fraction of inspired oxygen, lowest temperature, lowest serum pH, the occurrence of multiple seizures, and urine output (<1 ml/kg/h). The data collection window was the first 12 h from admission to the NICU with neonatal sepsis. During this period the above parameters were prospectively recorded. Higher scores indicate more severe illness. The severity of illness was arbitrarily graded according to the SNAP-II score as follows: mild: 1–20, moderate: 21–40, and severe: more than 40 . All patients in the sepsis group were followed up until discharge from the NICU or death. The key outcome measure was the difference in SNAP-II between survivors and nonsurvivors.
Blood samples were collected under completely sterile conditions from all patients for blood culture, hematological, and biochemical laboratory tests. Blood samples from neonates suspected of sepsis were withdrawn at the time of clinical diagnosis of sepsis, before initiation of antibiotic therapy. For all cases and control neonates included, CBC samples were collected in anti-coagulant EDTA tubes and CBC was performed immediately and the serum was separated following sample clotting in plain tubes by centrifugation and analyzed immediately for serum CRP. For cultures (only sepsis group), blood was inoculated into blood culture bottles with specific media.
CBCs of all patients were evaluated by an automated cell counter, Sysmex KX-21N (TAO Medical Incorporation, Toyama, Japan) . Total white blood cell count, total neutrophil count, RDW, platelet count, MPV, and PDW were noted. Peripheral blood smears were stained with Leishman stain for the determination of immature neutrophil count, immature to total neutrophil ratio . The HSS was determined for neonates in the sepsis group . CRP was measured by NycoCard Reader II. CRP levels less than 6 mg/dl were considered normal. Blood culture: 1–2 ml of blood was inoculated aseptically into the blood culture media after which the bottles were incubated at 37°C for 5–7 days. Positive blood cultures were subsequently subcultured on blood agar. The isolated microorganisms were identified by standard bacteriological methods.
The collected data were statistically analyzed using the Statistical Package for the Social Sciences (SPSS, SPSS Inc., Chicago, IL, USA) program for Windows, version 22. Quantitative results were presented as the mean±SD while qualitative data were presented by frequency distribution as percent (%). Student’s sample t test was used to compare between two means and χ2 test was used to compare proportions. Correlations were performed by using Pearson’s correlation coefficient (r). Receiver operating characteristic (ROC) curve analysis was performed to determine: the optimal cutoff values, the predictive performance of different studied markers and scores, and their sensitivities and specificities for the outcome. A probability of less than 0.05 was used as a cutoff point for all significant tests.
| Results|| |
In this study, no difference was noted in the perinatal data between the neonates diagnosed with neonatal sepsis and the control group regarding sex, gestational age, postnatal age, or weight ([Table 1]).
In the neonatal sepsis group, blood cultures were positive in 40 (62.5%) cases and negative in 24 (37.5%) cases ([Table 1]). The identified bacteria included: Staphylococcus aureus was found in 15 (23.4%) cases, Klebsiella spp. in 22 (34.3%) cases, Streptococcus pneumoniae in four (6.3%) cases, Escherichia More Details coli in 15 (23.4%) cases, Pseudomonas aeruginosa in four (6.3%) cases, and Entrobacter spp. in four (6.3%) cases.
The mean SNAP-II score for the neonatal sepsis group was 42.7±26.97 and their mean HSS was 4.28±0.94. We found significant differences between the neonatal sepsis group and the control group regarding their RDW, MPV, PDW, and CRP (P<0.0001 for all) ([Table 2]). On the other hand, when we compared the neonates with proven sepsis versus those with probable sepsis, we did not find statistically significant differences in their hematological markers nor in their SNAP-II or HSS scores (P>0.05 for all) ([Table 3]).
|Table 2 Score for Neonatal Acute Physiology-II score, hematological scoring system, hematological markers, and C-reactive protein in neonates with sepsis versus the control group|
Click here to view
|Table 3 Score for Neonatal Acute Physiology-II score, hematological scoring system, hematological markers, and C-reactive protein in neonates with proven versus probable sepsis|
Click here to view
Pearson’s correlation analyses were adopted to test the relation of SNAP-II with HSS and the studied markers in the sepsis group, SNAP-II score correlated significantly and positively with HSS (r=0.39, P=0.002), RDW (r=0.5, P=0.0001), MPV (r=0.47, P=0.0001), and PDW (r=0.55, P=0.0001), but did not have a significant correlation with CRP (r=0.21, P=0.1).
On comparing the survivors with the nonsurvivors, they were comparable regarding sex, gestational age, postnatal age, and weight. However, the nonsurvivors had significantly higher mean SNAP-II score which was more than or equal to 40 in 75% of them, which was of statistical significance too (P<0.001 for both). RDW, MPV, and PDW were significantly higher in the nonsurvivors than the survivors (P<0.0001, P<0.0001, and P=0.01, respectively). But, the HSS and CRP levels did not differ significantly between survivors and nonsurvivors (P>0.05 for both) ([Table 4]).
|Table 4 Perinatal data, Score for Neonatal Acute Physiology-II score, hematological scoring system, hematological markers, and C-reactive protein in the neonates with sepsis according to their outcome|
Click here to view
ROC curves were plotted to demonstrate the performance of different variables in predicting mortality. RDW had the highest area under the curve (AUC of 0.80), with a sensitivity of 77.8% and a specificity of 76.2%, at a cutoff of more than or equal to 18%, followed by SNAP-II (AUC of 0.78, sensitivity 77.8%, specificity 76.2%, at a cutoff ≥40). The hematological marker following RDW was MPV (AUC of 0.78, sensitivity 61.1%, specificity 88.1%, at a cutoff of ≥10.5 fl), followed by PDW (AUC of 0.69, sensitivity 50%, specificity 85.7%, at a cutoff of ≥16.8 fl). HSS and CRP showed no prognostic value by ROC curve analysis, as P value more than 0.05 for both ([Figure 1]).
|Figure 1 Multiple comparison receiver operating characteristic (ROC) curve analysis for the prediction of mortality among the studied cases of neonatal sepsis.|
Click here to view
| Discussion|| |
Neonatal sepsis has wide variations of clinical presentations. These presentations may be nonspecific and do not necessarily reflect the severity of the course or the possible outcome of the disease. In this study, we tried to determine the significance of feasible hematological investigations and HSS in predicting the outcome in neonates admitted with neonatal sepsis syndrome. This may help the clinicians to determine which of those neonates need closer monitoring.
RDW and platelet morphological parameters (MPV and PDW) in this study were significantly higher in the sepsis group than the control. This verifies the diagnostic role of these markers in neonatal sepsis, and is in accordance with a recent study by Zhang et al. .
The increase in the RDW was assumed to represent an integrative measure of the multiple harmful pathologic processes, including inflammation and oxidative stress, that simultaneously occur in sepsis . The proinflammatory cytokines released during sepsis have been found to inhibit erythropoietin-induced erythrocyte maturation and proliferation, and downregulate erythropoietin receptor expression, which are associated with RDW increases . And high oxidative stress occurring in sepsis generates reactive oxygen species  that reduces red blood cell survival and increases the release of large premature red blood cells into the peripheral circulation that also contributes to an increase in RDW .
The increase in platelet size (MPV) was attributed to bone marrow response to sepsis evolution , as MPV was considered a reflection of both proinflammatory and prothrombotic conditions, where thrombopoietin and numerous inflammatory cytokines regulate thrombopoiesis , while the heterogeneity in platelet size (PDW) was imputed to swelling, destruction, and immaturity of platelets produced during systemic sepsis .
But we did not find these changes to differ significantly between culture-proven sepsis and probable sepsis neonates, indicating that the changes occurring in the RDW and the platelet morphology represent bone marrow response to the systemic pathological processes occurring in sepsis rather than an organism-specific response.
SNAP-II score is a simple and objective score for neonatal sepsis, known for its ability to predict organ dysfunction and mortality in NICUs . RDW, MPV, and PDW in this study had significant correlations with SNAP-II score, which highlights their prognostic role in neonatal sepsis.
RDW was significantly higher in the nonsurvivors than survivors, with a sensitivity of 77.8% for predicting mortality and a specificity of 76.2%, at a cutoff of more than or equal to 18%. Similar to our results Chen et al.  reported increased RDW in neonates with sepsis and septic shock and that RDW increase is closely associated with bad prognosis. Also, Kim et al.  noted an increased RDW during the first 72 h after hospitalization in patients with severe sepsis or septic shock, and that this was associated with adverse clinical outcomes.We found MPV and PDW to be significantly higher in the nonsurvivors than the survivors. This was in accordance with previous studies ,, and in discordance with others ,. Furthermore, this study found that MPV and PDW showed significant mortality prognostic values. The association between platelet morphological changes and mortality in sepsis may be imputed to the hazardous integration of inflammation and hypercoagulability .
Sepsis was confirmed when HSS was equal to or greater than three . But, the HSS did not differ between survivors and nonsurvivors in this study and its ROC curve for the prediction of mortality was of statistical insignificance (P>0.05), which confines its role to early diagnosis of neonatal sepsis. Thus, the morphological changes occurring in red blood cells and platelets in response to neonatal sepsis have more prognostic value than the HSS which depends on platelet count and changes in count and maturity of white blood cells, especially neutrophils.
Although CRP was related to sepsis in this study, it was not related to the outcome nor to SNAP-II score. This limits prognostic role of CRP, confirming its well-known diagnostic ability.
| Conclusion|| |
We can conclude that RDW at levels more than or equal to 18% was the most sensitive hematological marker to predict mortality. Its sensitivity was similar to having an SNAP-II score more than 40. Platelet parameters had significant mortality prognostic values too. So, RDW, MPV, and PDW are quickly and easily available parameters in all hospitals and especially in those in developing countries and they can be used by clinicians as cost-effective markers to predict the outcome in neonatal sepsis syndrome. Regarding the HSS, its use should be reserved for diagnosis rather than prognosis of neonatal sepsis.
There are several limitations in this study. For example, repeated RDW, MPV, and PDW should have been assessed during the stay of the neonates till discharge or death, but the objective of this study was to determine the prognostic value of the studied markers at the time of diagnosis of neonatal sepsis. Further studies may address the relation of these markers to organ dysfunction occurring in neonatal sepsis and sepsis morbid outcomes other than death.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am
Thaver D, Zaidi AK. Burden of neonatal infections in developing countries: a review of evidence from community-based studies. Pediatric Infect Dis J
Richardson DK, Gray JE, McCormick MC, Workman K, Goldmann DA. Score for neonatal acute physiology: a physiologic severity index for neonatal intensive care. Pediatrics
Richardson DK, Corcoran JD, Escobar GJ, Lee SK. SNAP-II and SNAPPE II: Simplified newborn illness severity and mortality risk scores, for the Canadian NICU network, The Kaiser Permanente Neonatal minimum data set wide area network, and the SNAP-II study group. J Pediatr
Kasperska‑Zajac A, Grzanka A, Jarzab J, Misiołek M, Wyszyńska‑Chłap M, Kasperski J, Machura E. The association between platelet count and acute phase response in chronic spontaneous urticaria. Biomed Res Int
Ku NS, Kim HW, Oh HJ, Kim YC, Kim MH, Song JE et al.
Red blood cell distribution width is an independent predictor of mortality in patients with gram‑negative bacteremia. Shock
Celik A, Aydin N, Ozcirpici B, Saricicek E, Sezen H, Okumus M et al.
Elevated red blood cell distribution width and inflammation in printing workers. Med Sci Monit
Ren H, Hua Q, Quan M, Chen H, Hou H, Wang L et al.
Relationship between the red cell distribution width and the one-year outcomes in Chinese patients with stable angina pectoris. Intern Med
Allen LA, Felker GM, Mehra MR, Chiong JR, Dunlap SH, Ghali JK et al.
Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure. J Card Fail
Wang F, Pan W, Pan S, Ge J, Wang S, Chen M. Red cell distribution width as a novel predictor of mortality in ICU patients. Ann Med
Wiwanitkit V. Plateletcrit, mean platelet volume, platelet distribution width: its expected values and correlation with parallel red blood cell parameters. Clin Appl Thromb Hemost
Gulcu E, Durmaz Y, Karabay O. Effect of severe sepsis on platelet count and their indices. African Health Sci
Khair KB, Rahman MA, Sultana T, Roy CK, Rahman MQ, Shahidullah M, Ahmed AN. Role of hematologic scoring system in early diagnosis of neonatal septicemia. BSMMU J
Elghetany MT, Banki K. Erythrocytic disorders. In McPherson RA, Pincus MR, eds. Henry’s clinical diagnosis and management by laboratory methods
. 22nd ed. Philadelphia, PA: Elsevier/Saunders 2011. chap 32
Dacie VJ, Lewis SM. Preparation and staining method for blood and bone marrow films. In Dacie VJ, Lewis SM eds. Practical hematology
. 8th ed. Edinburgh: Churchill Livingstone 1994. 83–96
Rodwell RL, Leslie AL, Tudehope DI. Early diagnosis of neonatal sepsis using a hematologic scoring system. J Pediatr
Zhang HB, Chen J, Lan QF, Ma XJ, Zhang SY. Diagnostic values of red cell distribution width, platelet distribution width and neutrophil-lymphocyte count ratio for sepsis. Exp Ther Med
Kim CH, Park JT, Kim EJ, Han JH, Han JS, Choi JY et al.
An increase in red blood cell distribution width from baseline predicts mortality in patients with severe sepsis or septic shock. Crit Care
Pierce CN, Larson DF. Inflammatory cytokine inhibition of erythropoiesis in patients implanted with a mechanical circulatory assist device. Perfusion
Kolls JK. Oxidative stress in sepsis: a redox redux. J Clin Invest
Ghaffari S. Oxidative stress in the regulation of normal and neoplastic hematopoiesis. Antioxid Redox Signal
Becchi C, Al Malayan M, Fabbri LP, Marsili M, Boddi V, Boncinelli S. Mean platelet volume trend in sepsis: is it a useful parameter? Minerva Anestesiol
Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD. Mean platelet volume: a link between thrombosis and inflammation? Curr Pharm Des
Gao Y, Li Y, Yu X, Guo S, Ji X, Sun T et al.
The impact of various platelet indices as prognostic markers of septic shock. PLoS ONE
Helal NF, Samra NM, Abdel Ghany EAG, Said EA. Can the score for neonatal acute physiology II (SNAPII) predict morbidity and mortality in neonates with sepsis? J Neonatal Biol
Chen J, Jin L, Yang T. Clinical study of RDW and prognosis in sepsis new borns. Biomed Res
Catal F, Tayman C, Tonbul A, Akça H, Kara S, Tatli MM et al.
Mean platelet volume (MPV) may simply predict the severity of sepsis in preterm infants. Clin Lab
Akarsu S, Taskin E, Kilic M, Ozdiller S, Gurgoze MK, Yilmaz E, Aygun AD. The effects of different infectious organisms on platelet counts and platelet indices in neonates with sepsis: is there an organism-specific response? J Trop Pediatr
Golwala ZM, Shah H, Gupta N, Sreenivas V, Puliyel JM. Mean platelet volume (MPV), platelet distribution width (PDW), platelet count and plateletcrit (PCT) as predictors of in-hospital paediatric mortality: a case-control study. Afri Health Sci
Ahmad MS, Waheed A. Platelet counts, MPV and PDW in culture proven and probable neonatal sepsis and association of platelet counts with mortality rate. J Coll Physicians Surg Pak
Manucha V, Rusia U, Sikka M, Faridi MMA, Madan N. Utility of haematological parameters and C-reactive protein in the detection of neonatal sepsis. J Paediatr Child Health
[Table 1], [Table 2], [Table 3], [Table 4]