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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 2  |  Page : 581-587

Meanplatelet volume and serum uric acid in neonatal sepsis


1 Department of Pediatric, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt
2 Department of Biochemistry, Faculty of Medicine, Menoufia University, Shebin El-Kom, Egypt
3 Department of Pediatric, Shebin El-Kom Teaching Hospital, Shebin El-Kom, Egypt

Date of Submission07-Nov-2016
Date of Acceptance02-Mar-2017
Date of Web Publication25-Sep-2017

Correspondence Address:
Tamer W El-Zayat
Berket El-Sabae, Menoufia, 32511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_608_16

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  Abstract 

Objectives
The aim of this article was to determine the role of mean platelet volume(MPV) and uric acid(UA) level in the diagnosis of neonatal sepsis.
Background
MPV is a measure of platelet volume; larger platelets have more granules. It reveals the presence of inflammatory burden and disease activity in many diseases. UA is one of the most important antioxidants in human biological fluids and is responsible for neutralizing more than 50% of the free radicals in human blood. For this reason, it was thought that the antioxidant effects of UA could increase the life expectancy and/or reduce the incidence of malignancy.
Patients and methods
This study was conducted on 80 newborns divided into two groups: group1 included 40 newborns diagnosed with neonatal sepsis and group2 included 40 healthy newborns assigned as controls. All patients in the study were subjected to adequate assessment of history, full clinical examination, complete blood count including MPV, C-reactive protein, blood culture, and serum UA level at the time of diagnosis of sepsis.
Results
Septic neonates showed statistically higher values of MPV and statistically lower levels of serum UA. Area under curve values for MPV and UA were 0.65.4(P=0.01) and 0.69(P=0.001), respectively. The diagnostic cut-off values of MPV and UA for neonatal sepsis were 7.85 fl and 5.8mg/dl, respectively.
Conclusion
MPV and UA should be assessed in the early diagnosis of neonatal sepsis.

Keywords: diagnosis, mean platelet volume, newborn, sepsis, uric acid


How to cite this article:
El-Mashad GM, El-Sayed HM, Rizk MS, El-Hefnawy SM, El-Zayat TW. Meanplatelet volume and serum uric acid in neonatal sepsis. Menoufia Med J 2017;30:581-7

How to cite this URL:
El-Mashad GM, El-Sayed HM, Rizk MS, El-Hefnawy SM, El-Zayat TW. Meanplatelet volume and serum uric acid in neonatal sepsis. Menoufia Med J [serial online] 2017 [cited 2019 Aug 19];30:581-7. Available from: http://www.mmj.eg.net/text.asp?2017/30/2/581/215472


  Introduction Top


Sepsis is recognized as one of the most severe pathologies in newborns and young infants[1], responsible for almost one and half million deaths each year, worldwide[2].

Up to 10% of infants have infections in the first month of life, which causes 30–50% of total neonatal deaths in developing countries[2]. It is considered as the single most important cause of death [3] accounting for up to 50% of neonatal mortality[4]. For many years, a search has been ongoing to find predictors for neonatal sepsis that identify effectively patients who are at risk of infection [5]

Mean platelet volume(MPV) is the measurement of the average size of platelets found in the blood. Higher MPVs have been found in sepsis[6].

The increase in MPV could indicate either the development of a more invasive infection or the presence of an infection unresponsive to antibiotic therapy[7].

Uric acid(UA) has important antioxidant properties invitro, as it scavenges free radicals and chelates iron, the latter preventing iron-catalyzed oxidation. There is a strong correlation between the concentration of UA in biologic fluids and demonstrable antioxidant activity. Indeed, UA contributes to as much as 60% of free-radical scavenging in human serum[8].

Free radicals have been implicated in the pathogenesis of neonatal septicemia; neonates with septicemia had significantly lower levels of serum UA[9].


  Patients and Methods Top


After approval of the Local Institutional Ethical Committee of Menoufia University Hospital, and obtaining written consents from all patients to participate in our study, this study was carried out in the neonatal intensive care unit of Shebin El-Kom teaching hospital, during the period from May 2015 to May 2016.

The neonates were divided into two groups: group1 (patient group) included 40 neonates diagnosed with neonatal sepsis on the basis of clinical and laboratory data. Group2(control group) included 40 apparently healthy neonates with no clinical signs or laboratory evidence of sepsis.

This study was carried out on full-term neonates and preterm neonates.

Exclusion criteria of cases were severe congenital anomalies, dysmorphic features suggestive of chromosomal abnormalities, intrauterine growth retardation, perinatal asphyxia, and infants of diabetic mothers.

For all neonates, the following were performed:

  • Complete history taking to detect risk factors for sepsis included obstetric history(death of a previous sibling, previous admission to neonatal intensive care unit, etc.), Prenatal history[diabetes mellitus, maternal fever>38°C, maternal antibiotics, maternal urinary tract infection(UTI), etc.], natal history[premature rupture of membrane(PROM), maternal fever, prolonged second stage of labor, etc.], postnatal history(low Apgar score at 1 and 5min, aggressive resuscitation, respiratory distress, cyanosis, fever, jaundice, etc.), and current history, which included most common symptoms of sepsis.
  • A thorough clinical examination included assessment of gestational age using the new Ballard score, Birth weight measurement, detection of clinical signs of sepsis such as temperature instability (<37 or>38.5°C), respiratory dysfunction (apnea, intercostal retraction, increased oxygen requirement, signs of respiratory distress), circulatory dysfunction (poor peripheral circulation, hypotension, tachycardia, shock, prolonged capillary refill), gastrointestinal tract dysfunction(abdominal distension, bloody stool, feeding intolerance, hepatomegaly, jaundice), neurological dysfunction(irritability, hypotonia, lethargy), hypoglycemia, hyperglycemia, petechiae, bleeding(with thrombocytopenia), or disseminated intravascular coagulopathy.
  • Laboratory investigations at the time of diagnosis of sepsis included complete blood cell count with differential leukocytic count and MPV, C-reactive protein(CRP) quantitative assay, blood culture, serum UA measurement: blood samples were collected aseptically by venipuncture once from controls and cases, the blood was left to clot, and then centrifuged for 10min at 5000rpm. UA was determined by enzymatic colorimetric test, using the Uric acid kits (SPINREACT, Santa Coloma) [10].


Statistical analysis

All data were collected, tabulated, and statistically analyzed using SPSS 19.0 for Windows(SPSS Inc., Chicago, Illinois, USA) and MedCalc 13 for Windows(MedCalc Software bvba, Ostend, Belgium).


  Results Top


This study showed that there was no significant difference between the patient group and the control group with regard to sex, mode of delivery, and gestational age. Birth weight and Apgar scores at 1 and 5min were highly significantly lower in the patient group compared with the control group[Table1].
Table 1: Demographic data of the study groups

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It was also found that in the patient group, prematurity was the highest risk factors for sepsis(70%), followed by umbilical catheterization(25%), PROM (25%), mechanical ventilation(20%), UTI(15%), chorioamnionitis(10%), and abruptio placenta(5%) [Table2].
Table 2: Risk factors for neonatal sepsis in the patient group

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It was also observed that 77.5% of cases had feeding intolerance, 75% developed respiratory distress, 70% developed lethargy, 50% had poor perfusion, 48.7% had temperature instability, 45% had abdominal distention, 37.5% developed seizures, 32.5% had hypotension, and 12.5% developed hypotonia[Figure 1].
Figure 1: Percentages of clinical manifestations of neonatal sepsis in the patient group.

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In addition, there were highly significant decreases in hemoglobin, red blood cells, and platelets count in the patient group compared with the control group. Also, there were highly significant increases in white blood cells, the immature/total neutrophil(I/T) ratio, absolute neutrophil count, and CRP in the case group compared with the control group[Table3].
Table 3: Comparison of laboratory parameters among the study groups

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Moreover, 52.5% of the patient group(21 newborns) had a positive blood culture: 20% of them were positive for Klebsiella spp., 15% were positive for Candida spp., 7.5% were positive for Acinetobacter spp. and Pseudomonas spp., 2.5% were positive for methicillin-resistant Staphylococcusaureus, whereas 47.5% of them had negative blood cultures[Figure 2].
Figure 2: The percentage of cases based on the results of blood culture.

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There was a highly significant increase in MPV in the patient group than in the control group[Figure 3] and there was a highly significant decrease in serum UA in the patient group than in the control group[Figure 4].
Figure 3: Comparison between the mean platelet volume in the patient group and the control group.

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Figure 4: Comparison between serum uric acid in the patient group and the control group.

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Area under curve values obtained from ROC analysis for MPV and UA were 0.65.4(P=0.01) and 0.69(P=0.001), respectively. The diagnostic cut-off values of MPV and UA for neonatal sepsis were 7.85 fl and 5.8mg/dl, respectively[Table4].
Table 4: Predictive values of mean platelet volume and uric acid levels

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This study showed that MPV showed a significant positive correlation with the I/T neutrophil ratio and CRP and had a significant negative correlation with gestational age, birth weight, platelet count, and UA[Table5].
Table 5: Correlation between mean platelet volume and other measured parameters in the study groups

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Also, UA showed a significant positive correlation with the platelet count and a significant negative correlation with the I/T neutrophil ratio, MPV, and CRP[Table6].
Table 6: Correlation between serum uric acid and other measured parameters in the study group

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  Discussion Top


It is estimated that four million neonatal deaths occur worldwide every year, and~one-third of these are caused by infections. Sepsis and bacterial meningitis continue to be one of the main causes of neonatal mortality, especially among very low birth weight newborn infants[11].

Early diagnosis and treatment of the newborn infant with suspected sepsis are essential to prevent severe and life-threatening complications. Compared with the clear and valuable therapeutic options, the diagnosis of suspected neonatal sepsis is challenging. In preterm infants, the diagnosis of sepsis is more difficult because of the nonspecific clinical presentation and lack of reliable diagnostic tests[12].

In the current study, it was found that lower birth weight was significantly associated with increased frequency of sepsis. This was also observed in several other studies[13],[14],[15],[16]. As low birth weight newborns have inappropriate immunological response, they have low levels of various complement systems and poor mucosal defenses. Birth weight less than 1000g increases the neonatal infection rate by 26 folds when compared with full-term infants[16].

In the current study, it was found that Apgar scores at 1 and 5min were highly significantly lower in the cases group than in the control group. This agrees with several studies, which observed that a 5-min Apgar score less than 7 carries a significantly higher risk of sepsis than infants with higher scores and that Apgar score less than 5 at one minute may be due to sepsis, especially with the presence of risk factors for infection[17],[18].

Furthermore, low Apgar scores usually necessitate more prolonged and aggressive resuscitation, which is a known risk factor for sepsis[15].

In the current study, it was found that the mode of delivery was not significantly associated with increased frequency of sepsis. This is in agreement with other studies[19],[20].

Regarding risk factors for neonatal sepsis, we found that prematurity was the highest risk factor in the case group(70%), followed by PROM(25%), umbilical catheterization(25%), mechanical ventilation(20%), maternal UTI(15%), chorioamnionitis(10%), and abruptio placenta(2%). This agrees with the result of several studies[13],[21].

In the present study, clinical evaluation of neonates with sepsis revealed that feeding intolerance(77%), respiratory distress(75%), lethargy(70%), poor perfusion(50%), temperature instability(48.7%), abdominal distention(45%), seizures(37.5%), and hypotension(32.5%) were the most common clinical presentations. This is in agreement with another study that described them as the major clinical presentations of sepsis[20].

In this study, there was a significant decrease in hemoglobin level, red blood cell count, and platelet count and a significant increase in the white blood cell count, the I/T ratio, absolute neutrophil count and MPV in the patient group compared with the control group. This is correlated with the results of several studies[22],[23].

In the current study, CRP was significantly higher in cases than in controls, which is in agreement with the results of other studies[24],[25],[26]. CRP is one of the acute phase reactants that are synthesized in liver in response to trauma or invasion of microorganisms[27].

Regarding the type of bacteria isolated from blood cultures in the present study, 21(52.5%) cases had positive culture results and 19(47.5%) patients had negative culture results.

Similar results have been found in the study of Hisamuddin etal.[24], who found that culture-proven sepsis occurred in 30% of their cases with sepsis.

In addition, EdmondandZaidi [28] stated that identification of pathogenic organisms in neonates with sepsis syndrome presents some difficulties. The bacterial load may be low due to mothers receiving antepartum or intrapartum antibiotics and because only small amounts of blood can often be taken from newborns. Contamination rates may also be very high due to the technical difficulties of sterile venipuncture in small babies. There may also be misinterpretation of the role of coagulase-negative staphylococci(e.g.S.epidermidis), as these organisms are both normal skin flora and pathogenic organisms in preterms and infants with indwelling blood vessel catheters.

In the present study, Klebsiella pneumoniae was the most common organism isolated in the positive blood cultures, followed by Candida albicans(20 and 15%, respectively), and the least common organisms were Acinetobacter spp.(7.5%), Pseudomonas spp.(7.5%), and methicillin-resistant Staphylococcusaureus(2.5%).

This is in agreement with another study in which the most common organism in positive blood cultures was K.pneumoniae [29].

In the current study, it was found that MPV was significantly higher in patients than in controls.

This is in agreement with the study of Aydin etal.[30], who found that MPV was significantly higher in newborns with septicemia than in the control group.

Similar results were found by Oncel etal.[31], who studied MPV in neonatal sepsis and found that there was a statistically significant difference with regard to baseline MPV values between patients with sepsis.

This disagrees with the study of Aksoy etal.[32], who found that there was no significant difference in MPV between septic and control infants. This disagreement may be due to differences in the demographic data of the studied groups as they focused on MPV in the sepsis of very low birth weight neonates.

In the current study, MPV showed a significant negative correlation with gestational age, birth weight, platelet count, and serum UA, whereas it showed statistically significant positive correlation with CRP and the I/T ratio.

This is in agreement with the work of Aydin etal.[30], who found negative correlations between MPV and gestational week(r=−0.24, P=0.000), birth weight(r=−0.27, P=0.000), platelet count(r=−0.18, P=0.002), and UA levels(r=−0.20, P=0.000). Positive correlations were found between MPV and the leukocyte count(r=0.11, P=0.04), and CRPvalues(r=0.32, P=0.000).

Our study revealed that the best cut-off value of MPV to detect sepsis was 7.85 fl, with 85% sensitivity and 43% specificity.

In the current study, it was found that serum UA was significantly lower in patients than in controls.

There are a large number of studies that investigate the association between neonatal sepsis and free oxygen radicals and antioxidants[33]. However, as far as the authors are concerned, there are three studies that focus on the association between neonatal sepsis and UA.

In their research, which included 30 neonates with sepsis and 20 neonates without sepsis, Batra etal. [34] demonstrated that UA levels were significantly lower in patients with sepsis. Similarly, Kapoor etal. [35] demonstrated, in their research comparing 44cases of newborns with sepsis with 84 healthy newborns, that the newborns with sepsis had lower UA levels.

Aydin etal. [30] compared 146cases of neonatal sepsis with 142 healthy newborns and found that the newborns with sepsis had lower UA levels.

In contrast to our study, Hooman etal. [36] showed that higher UA levels served as an additive risk factor in sepsis.

In the current study, serum UA showed a statistically significant positive correlation with platelet count, whereas it showed a statistically significant negative correlation with I/T ratio, MPV, and CRP.

This is in agreement with the work of Aydin etal.[30], who found positive correlations between UA levels and gestational week(r=0.20, P=0.000) and birth weight(r=0.22, P=0.000). UA levels were negatively correlated with CRPvalues(r = −0.210, P=0.000).

Our study revealed that the best cut-off value of serum UA to detect sepsis was 5.8mg/dl, with 75% sensitivity and 58% specificity.


  Conclusion Top


From the results of this study, we conclude that MPV increases significantly in neonates with sepsis, whereas serum UA decreases significantly in neonates with sepsis

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table1], [Table2], [Table3], [Table4], [Table5], [Table6]


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