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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 32  |  Issue : 2  |  Page : 126-130

Evaluation of mannose-binding lectin serum level in prediction of neonatal sepsis


1 Department of Pediatrics, Faculty of Medicine, Benha University, Benha, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Benha University, Benha, Egypt

Date of Submission16-Sep-2015
Date of Acceptance01-Nov-2015
Date of Web Publication14-Apr-2016

Correspondence Address:
Ibrahim M Mohamed
M.B.B.Ch, Mashtol El-kadi, Zagazig, Sharkeya, 44511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-208X.180325

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  Abstract 

Background
Despite improved neonatal care over the past decades, infections remain common and sometimes life threatening in neonates admitted to the neonatal ICU. Neonatal sepsis has the highest morbidity and mortality.
Objective
The aim of the study was to evaluate mannose-binding lectin (MBL) serum level as a marker for prediction of neonatal sepsis.
Patients and methods
This prospective case-control study was conducted on 90 neonates admitted to the neonatal ICU. The 90 neonates were divided into two groups: the patient group and the control group. The patient group included 45 cases with neonatal sepsis and the control group included 45 healthy neonates. Serum levels of MBL were measured by immunoassay. The results were tabulated and analyzed with SPSS.
Results
Serum MBL levels were significantly lower in the neonates with sepsis than in the control group (0.455 ± 0.245 vs. 1.212 ± 0.249 μg/ml; P < 0.001). The lowest MBL levels were detected in those infants with septic shock. MBL had high sensitivity (97.7%) and specificity (86.6%) as well as positive (88%) and negative (97.5%) predictive values to detect sepsis.
Conclusion and key messages
MBL serum level could be considered a sensitive and specific marker for prediction of neonatal sepsis. Neonates with significant decrease in MBL are at increased risk for developing sepsis and septic shock.

Keywords: Mannose-binding lectin, newborn infants, sepsis, septic shock


How to cite this article:
Amer ESA, El-Shaer OS, Mohamed IM. Evaluation of mannose-binding lectin serum level in prediction of neonatal sepsis. Benha Med J 2015;32:126-30

How to cite this URL:
Amer ESA, El-Shaer OS, Mohamed IM. Evaluation of mannose-binding lectin serum level in prediction of neonatal sepsis. Benha Med J [serial online] 2015 [cited 2017 Oct 21];32:126-30. Available from: http://www.bmfj.eg.net/text.asp?2015/32/2/126/180325


  Introduction Top


'Suspected sepsis' is one of the most common diagnoses made in the neonatal ICU (NICU). However, the signs of sepsis are nonspecific, and inflammatory syndromes of noninfectious origin mimic neonatal sepsis [1].

Most infants with suspected sepsis recover with supportive care (with or without initiation of antimicrobial therapy). The challenges for clinicians are three:

  1. Identifying neonates with a high likelihood of sepsis promptly and initiating antimicrobial therapy;
  2. Distinguishing 'high-risk' healthy-appearing infants or infants with clinical signs who do not require treatment; and
  3. Discontinuing antimicrobial therapy once sepsis is deemed unlikely [2].


Neonatal sepsis may be categorized as early onset or late onset. Of newborns with early-onset sepsis, 85% present within 24 h, 5% present at 24-48 h, and a smaller percentage present within 48-72 h. Onset is most rapid in premature neonates [3].

Mannose-binding lectin (MBL) is a plasma protein that plays an important role in innate immunity, and thus it is particularly important in neonates in whom adaptive immunity is not yet completely developed. Circulating MBL binds to carbohydrate structures on the surface of a wide range of microorganisms and thereby provides a first-line defense [4].

MBL bound to microorganisms activates the lectin pathway of the complement system. This leads to opsonization and enhanced phagocytosis [5]. Circulating MBL levels are determined genetically and may vary between 0 and 10 μg/ml [6].


  Patients and methods Top


We conducted this prospective case-control study on a patient group of 45 cases with neonatal sepsis and a control group of 45 healthy neonates at the NICU. The study was approved by the research ethics committee. Both preterm and full-term newborn infants were enrolled in the study. Informed parental consent was obtained for all babies in the study. Definitive sepsis was diagnosed if the patients had the combination of a positive blood culture and clinical and/or laboratory evidence of sepsis. Clinical markers of sepsis included poor circulation (pallor, hypotension, and tachycardia or bradycardia), increased oxygen requirements or ventilation parameters, temperature instability, lethargy or irritability, abdominal distension, and feeding intolerance. Laboratory markers included abnormal leukocyte count, increased I/T (immature to total neutrophil) ratio, low platelet count, and raised C-reactive protein. Infants with neonatal asphyxia, metabolic disease, or congenital malformations were excluded.

All cases underwent the following:

  1. History taking (to detect risk factors for sepsis): This included past history (previous sibling death, previous admission to NICU); prenatal history (diabetes mellitus, maternal fever >38°C, maternal antibiotics, maternal urinary tract infection (UTI)); natal history (premature rupture of membranes, maternal fever, prolonged second stage of labor); and postnatal history (low Apgar score at 1 and 5 min, aggressive resuscitation, respiratory distress, cyanosis, fever, jaundice).
  2. Thorough clinical examination: This included weight, length, head circumference, gestational age, vital signs (pulse, temperature, blood pressure, and respiratory rate), and clinical examination to detect signs of sepsis, such as temperature instability (< 37.0 or > 38.5°C), respiratory insufficiency [dyspnea, tachypnea (> 60 breaths/min), apnea, ventilation support, and increased oxygen requirement], cardiovascular dysfunction [tachycardia (>160 beats/min), bradycardia (<100 beats/min), hypotension (diastolic blood pressure < 40 mmHg), and need for vasopressor support or inotropic medication], neurological irregularities (hypotonia and lethargy or irritability), and gastrointestinal problems (feeding intolerance, vomiting, abdominal distension, suspicion of necrotizing enterocolitis).
  3. Laboratory investigations: This included complete blood count, differential white blood cell count, platelet count, C-reactive protein, blood culture, and serum MBL.


Blood culture steps

  1. Perform a sterile venous puncture.
  2. Add 1 ml of blood to 9 ml of nutrient broth.
  3. Incubate at 37°C for 1-7 days.
  4. Observe daily for any turbidity, surface pellicle, or grayish deposits.
  5. If any of the above are found subculture on blood agar plate.
  6. Incubate at 37°C for 24 h.
  7. Next day, gram stain for isolated colonies.
  8. Apply an antibiotic sensitivity disk.


Measurement of serum mannose-binding lectin level

Serum levels of MBL were measured using an immunoassay (MBL oligomer ELISA, Antibody Shop ELISA kit; Eagle Biosciences, Berlin, Germany) according to the manufacturer's protocol. Blood samples were collected aseptically from all neonates, were left to clot for 30 min, and centrifuged. The sera were separated and stored at −20°C until the time of the assay.

Statistical analysis

All data were analyzed using SPSS 18.0 for Windows (IBM, Endicott, Broome County, New York, USA) and MedCalc 13 for Windows (MedCalc Software bvba, Ostend, Belgium). Continuous variables were expressed as mean ± SD, range, and median, and the categorical variables were expressed as numbers and percentages. Continuous variables were checked for normality by using the Shapiro-Wilk test. Independent-sample Student's t-test was used to compare two groups of normally distributed data, whereas the Mann-Whitney U-test was used for non-normally distributed data. The Kruskal-Wallis H-test was used to compare non-normally distributed data between more than two groups. Percentage of categorical variables were compared using the χ2 -test.

Receiver operating characteristic curve analysis was used to identify optimal cutoff values of MBL with maximum sensitivity and specificity for detection of neonatal sepsis. All tests were two sided.

P value less than 0.05 was considered statistically significant (S); P value less than 0.01 was considered highly statistically significant (HS); and P value of 0.05 and greater was considered statistically nonsignificant (NS).


  Results Top


The clinical characteristics of the study groups are summarized and illustrated in [Table 1] and [Figure 1]. There were highly significant differences between the patient group and the control group as regards vital signs, except for systolic blood pressure, which exhibited a significant difference.
Figure 1: Vital signs of the studied groups.

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Table 1: Vital signs of the studied groups

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Our results showed that the total leukocyte count, absolute neutrophil count, I/T ratio, and C-reactive protein were significantly higher in patients than in the control group. However, platelet counts were significantly lower in infected infants than in the control group, as shown in [Table 2].
Table 2: Laboratory findings of the studied groups

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Our results show a highly significant relation in the patient group between the serum level of MBL, gestational age, and outcome and a nonsignificant relation between the serum level of MBL, the age at onset of sepsis, and blood culture, as shown in [Table 3].
Table 3: Relation between mannose-binding lectin and various study parameters in the patient group (N = 45)

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[Table 4] shows that MBL had high sensitivity (97.7%), specificity (86.6%), and positive (88%) and negative (97.5%) predictive values to detect sepsis [Figure 2].
Figure 2: Receiver operating characteristic (ROC) curve of white blood cells (WBCs), I/T ratio, C-reactive protein (CRP), and mannose-binding lectin (MBL) as markers for neonatal sepsis.

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Table 4: White blood cells, I/T ratio, C-reactive protein and mannose-binding lectin as markers for neonatal sepsis

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  Discussion Top


Neonatal sepsis is the leading cause of death in critically ill patients in the USA. It develops in 750 000 people annually, and more than 210 000 of them die. About 9% of neonates with sepsis progress to severe sepsis, and 3% progress to septic shock [7].

In neonates, low serum MBL levels are associated not only with variant MBL2 genotype but also with low gestational age. Detection of MBL deficiency at birth should be based on actual MBL plasma levels rather than on MBL2 genotype [8].

Our results showed highly significant differences between the patient group and the control group as regards vital signs, white blood cell count, platelet count, I/T ratio, C-reactive protein level, MBL level, blood culture, and outcome, and nonsignificant difference as regards hypertension and gestational age.

Our results also showed nonsignificant differences between full-term and preterm patients as regards the selected study parameters, except for gestational age and MBL level, which exhibited significant differences. There were highly significant differences between full-term patients and full-term controls as regards the selected study parameters, except for gestational age and Apgar score at 5 min, which exhibited nonsignificant differences.

El-Shimi and colleagues (2010) stated that the mean MBL plasma level was found to be lower in preterm than in full-term neonates; yet this difference did not reach statistical significance. There was a negative correlation between MBL level and gestational age. The deficient group had higher incidence of sepsis than the nondeficient group. A highly significant positive correlation was demonstrated between MBL plasma level in neonatal and umbilical cord blood samples. Thus, premature neonates have low MBL serum levels, which could be measured in either their venous or umbilical cord blood efficiently [9].

Mohamed and Saeed (2012) stated that MBL levels were significantly lower in infants with sepsis than in the control group. The lowest MBL levels were detected in those infants with septic shock, particularly in those who died. MBL had high sensitivity, specificity, and positive and negative predictive values to detect sepsis. Thus, low MBL serum levels could be considered a sensitive and specific marker for predicting sepsis, septic shock, and their clinical outcomes in newborn infants [10].


  Conclusion Top


MBL serum level could be considered a sensitive and specific marker for prediction of neonatal sepsis. Neonates with significant decrease in MBL are at increased risk of developing sepsis and septic shock.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, et al., Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics 2010; 126 :443-456.  Back to cited text no. 1
    
2.
Polin RA. The Committee on Fetus and Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics 2012; 129 :1006-1015.   Back to cited text no. 2
    
3.
Klinger G, Levy I, Sirota L, Boyko V, Reichman B, Lerner-Geva L. Epidemiology and risk factors for early onset sepsis among very-low-birthweight infants. Am J Obstet Gynecol 2009; 201 :38.e1-38.e6.   Back to cited text no. 3
    
4.
Dommett RM, Klein N, Turner MW. Mannose-binding lectin in innate immunity: past, present and future. Tissue Antigens 2006; 68 :193-209.  Back to cited text no. 4
    
5.
Brouwer N, Dolman KM, van Zwieten R, Nieuwenhuys E, Hart M, Aarden LA, et al. Mannan-binding lectin (MBL)-mediated opsonization is enhanced by the alternative pathway amplification loop. Mol Immunol 2006; 43 :2051-2060.  Back to cited text no. 5
    
6.
Frakking FN, Brouwer N, van Eijkelenburg NK, Merkus MP, Kuijpers TW, Offringa M, Dolman KM Low mannose-binding lectin (MBL) levels in neonates with pneumonia and sepsis. Clin Exp Immunol 2007; 150 : 255-262.  Back to cited text no. 6
    
7.
Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000, N Engl J Med 2003; 348 : 1546-1554.  Back to cited text no. 7
    
8.
Frakking FN, Brouwer N, Zweers D, Merkus MP, Kuijpers TW, Offringa M, Dolman KM High prevalence of mannose-binding lectin (MBL) deficiency in premature neonates. Clin Exp Immunol 2006; 145 :5-12 .  Back to cited text no. 8
    
9.
El-Shimi MS, Khafagy SM, Abdel-al H, Omara MA. Mannose-binding lectin deficiency in preterm neonates. Egypt J Pediatr Allergy Immunol 2010; 8 :75-80.  Back to cited text no. 9
    
10.
Wahab Mohamed WA, Saeed MA. Mannose-binding lectin serum levels in neonatal sepsis and septic shock. J Matern Fetal Neonatal Med 2012; 25 : 411-414.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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