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ORIGINAL ARTICLE
Year : 2018  |  Volume : 31  |  Issue : 4  |  Page : 1428-1434

Blood eosinophil levels in newborns with severe indirect hyperbilirubinemia treated with phototherapy


1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Pediatrics, Menouf Hospital, Menouf, Menoufia, Egypt

Date of Submission01-Nov-2016
Date of Acceptance11-Dec-2016
Date of Web Publication14-Feb-2019

Correspondence Address:
Asmaa M Tolba
Menoufia, El Menoufiya Governorate
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.252070

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  Abstract 


Objective
The aim of this study was to investigate the effect of phototherapy on peripheral eosinophil counts in newborns with severe indirect hyperbilirubinemia needing phototherapy.
Methods We conducted a search of Medline databases (PubMed, Medscape, ScienceDirect) and all materials available on the Internet. The initial search presented one articles that met the inclusion criteria. The articles studied the relation between peripheral eosinophil count and exposure to phototherapy. If the studies did not fulfill the inclusion criteria, they were excluded. Studies were assessed for whether ethical approval had been obtained, eligibility criteria has been specified, appropriate controls had been considered, adequate information had been provided, and assessment measures had been defined. Comparisons were made by means of structured review with the results tabulated.
Results
The study was conducted on 30 neonates suffering from severe indirect hyperbilirubinemia who served as the patient group and another 30 neonates who were normal and served as the control group. It was found that there was an increase in peripheral eosinophil count in neonates who were treated with phototherapy for 48–72 h.
Conclusion
Peripheral eosinophil count may be affected by phototherapy. The exact mechanism of neonatal jaundice/phototherapy and later risk of developing asthma is not clear yet, and further prospective studies in larger groups are needed. Neonatologists should concentrate on underlying problems, as eosinophilia is sometimes clinically insignificant with regard to morbidity and requires no specific treatment. In fact, it may be indirect evidence of clinical recovery. Unless eosinophilia is associated with clinical symptomatology, medical evaluation should be limited to routine follow-up examinations and repeat monitoring of absolute eosinophil counts.

Keywords: hyperbilirubinemia, peripheral eosinophil count, phototherapy


How to cite this article:
El Mashad GM, El Sayed HM, Tolba AM. Blood eosinophil levels in newborns with severe indirect hyperbilirubinemia treated with phototherapy. Menoufia Med J 2018;31:1428-34

How to cite this URL:
El Mashad GM, El Sayed HM, Tolba AM. Blood eosinophil levels in newborns with severe indirect hyperbilirubinemia treated with phototherapy. Menoufia Med J [serial online] 2018 [cited 2024 Mar 28];31:1428-34. Available from: http://www.mmj.eg.net/text.asp?2018/31/4/1428/252070




  Introduction Top


Jaundice is the most common clinical diagnosis in neonatal medicine and is caused by elevated unconjugated (indirect) and/or conjugated (direct) bilirubin level[1].

Bilirubin is one of the end products of heme catabolism, which is mediated by heme oxygenase and biliverdin reductase[2]. Even though it is known that bilirubin has toxic effects, it also has antioxidant properties and protects the lungs and even the intestines[3]. Moreover, bilirubin inhibits vascular cell adhesion molecule-1 (VCAM-1)-dependent mechanisms[4]. VCAM-1 plays a major role in inflammatory cell migration and is located on the endothelial cell surface; it facilitates the adhesion of lymphocytes and eosinophils to the vascular endothelium[5]. Keshavan et al.[6] utilized a mouse model of airway inflammation similar to asthma, and they discovered VCAM-1-mediated pulmonary eosinophilia, lymphocytosis, and anti-inflammatory effects of bilirubin in the lung tissue and eosinophilia in the circulation of these mice.

Fortunately, phototherapy at a wavelength of 425–475 nm is an effective method for the prevention and treatment of neonatal indirect hyperbilirubinemia[7].

Phototherapy may be associated with some long-term side effects such as melanocytic nevi, skin cancer, allergic diseases, patent ductus arteriosus, and retinal damage[8].

Eosinophil granulocytes, usually called eosinophils or acidophils, are white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates along with mast cells. They also control mechanisms associated with allergy and asthma. They are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood[9].

Eosinophils, along with basophils and mast cells, are important mediators of allergic responses and asthma pathogenesis and are associated with disease severity[10],[11].


  Methods Top


Search strategy

This study focused on the neonates in Menouf Hospital in the period between April 2015 and March 2016. The study was conducted on 60 term and near-term neonates who were divided into two groups: group I consisted of cases (30 neonates) and group II (30 neonates) served as the control group. The infants had been admitted to the neonatal ICU of Menouf Hospital.

This study was approved by the ethics committee of the Faculty of Medicine, Menoufia University.

Ethical considerations

  1. Written informed consent was obtained from the parents of all patients before enrolling them in the study
  2. The steps of the study, the aims, the potential benefits and hazards, all were discussed with the parents
  3. Confidentiality of data was ensured
  4. The parents had the right to withdraw their children from the study at any time without giving any reasons.


Study selection

All the neonates were independently assessed for inclusion. They were included if they fulfilled the following criteria:

Inclusion criteria of the neonates: All newborn infants were eligible for inclusion in this study if they were of gestational age 37 weeks or more and had a birth weight of 2000 g or more and required phototherapy in the first week of life according to the hour-specific total bilirubin values as follows:

  1. 24 h of age: >12 mg/dl (205 μmol/l)
  2. 48 h of age: >15 mg/dl (257 μmol/l)
  3. 72 h of age: >18 mg/dl (308 μmol/l).


Data extraction

Neonates with congenital malformations, congenital infections, birth asphyxia, or sepsis, those delivered by instrumental delivery (vacuum), those with cephalehematoma, and those suffering from starvation were excluded from the study.

All cases included in the study were subjected to the following:

The maternal history of all neonates, including maternal diseases (diabetes – autoimmune), Rh blood group, and premature rupture of membrane, was recorded.

The newborns were subjected to a meticulous systemic examination, including assessment of gestational age by Ballard score[11], anthropometric measurements, vital signs, and systemic examination with special emphasis on neurological examination, including activity, positioning, tone, reflexes, and cry.

Phototherapy procedure

With three standard phototherapy units containing two blue lamps (2 W/250, B6 model; Philips, 6th October city, Egypt) and two white lamps, which were 58.8 cm in length, 38 mm in diameter, and 57 V/0.38 Amp, conventional phototherapy was applied from three directions. The spectral irradiance was ~12 μW/cm2/nm. Phototherapy was applied continually after hospital admission at a 40 cm distance to the babies, who were completely nude except for a diaper, lying inside the incubator, with eyes covered with a special black-eye protection band. During the procedure, the babies were taken away from phototherapy only for feeding for 15–20 min every 3 h as well as for brief examination and blood collection. When TSB level decreased below 12 mg/dl, phototherapy application was discontinued.

Sampling

A volume of 5 ml of blood was obtained for routine and specific investigations; 2 ml was taken in EDTA tubes for evaluation of hemoglobin levels and blood group; 3 ml was taken in plain tubes. Serum was separated for bilirubin and C-reactive protein (CRP) evaluation, and 1 ml was taken to analyze eosinophil cell count before and after phototherapy.

Investigations

Routine investigations

  1. Determination of serum bilirubin:


  2. Serial serum bilirubin measurements were taken on a daily bases. Total direct serum bilirubin and indirect bilirubin were measured using a bilirubin photoanalyzer

  3. Blood group and Rh determination:


  4. The ABO and Rhesus blood grouping was done to rule out ABO and Rh incompatibility as the cause of jaundice

  5. Serum CRP:


  6. CRP was analyzed as a part of the septic workup to rule out infection as a cause of jaundice

  7. Determination of complete blood count:


  8. Total leukocyte count and differential leukocyte count were evaluated to rule out infection, red blood cell to rule out polycythemia, and hemoglobin% to rule out anemia or polycythemia. Peripheral smear was taken to determine the red blood cell morphology, and reticulocyte count was also evaluated by complete blood count, Dwarka, New Delhi-110075, India).


Specific investigations

All patients were subjected to eosinophil counts.

Principle

The eosinophil count was measured by diluting whole blood with a staining solution. The phyloxine B present in the diluting fluid stains only the eosinophils red; all other leukocytes are preserved but not stained. The diluted specimen is charged onto a hemacytometer for counting. On using a low-power (×10) objective, the eosinophils appear bright orange-red and are clearly distinguishable from neutrophils, basophils, lymphocytes, and monocytes, which do not stain.

Calculations

The same general formula used to calculate the leukocyte count is also applied for the eosinophil count. The variation will be in the dilution and volume factors (for the Fuchs-Rosenthal counting chamber). For eosinophil counts, the dilution is 1:32 and the volume counted is 6.4 ml. Calculate the eosinophil count for each Unopette and average the result (×109/l or/mm3).

Eosinophils/l = Number of eosinophils counted×correction for dilution (32) × correction for volume of the two chambers (1/6.4 μl) × 106.

Quality assessment

The quality of all studies was assessed. Important factors included study design, attainment of ethical approval, evidence of a power calculation, specified eligibility criteria, appropriate controls, adequate information, and specified assessment measures. It was expected that confounding factors would be reported and controlled for and appropriate data analysis made in addition to an explanation of missing data.

Data synthesis

A structured systematic review was performed with the results obtained.


  Results Top


Study selection and characteristics

Data were statistically described in terms of mean ± SD, median and range, or frequencies (number of cases) and percentages when appropriate. Comparison between days 1 and three values was made using the paired t-test. Comparison between the study groups was made using the Mann–Whitney U-test for independent samples. Correlation between various variables was determined using the Pearson's correlation coefficient for linear relation in normally distributed variables and the Spearman's rank correlation coefficient for non-normal variables/nonlinear monotonic relation. P values less than 0.05 were considered statistically significant. All statistical calculations were performed using statistical package for the social science (SPSS Inc., Chicago, Illinois, USA) release 15 for Microsoft Windows (2006) [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5],[Figure 6],[Figure 7].
Figure 1: Blood group distribution in the studied groups.

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Figure 2: Phototherapy distribution among cases.

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Figure 3: Exchange therapy distribution among cases.

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Figure 4: Intraveenous immunoglobulin distribution among cases.

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Figure 5: Laboratory investigations of cases before and after phototherapy.

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Figure 6: Correlation between total bilirubin and eosinophil before phototherapy.

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Figure 7: Correlation between total bilirubin and eosinophil after phototherapy.

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Neonatal history of the studied groups

There was significant difference between the studied groups regarding blood groups and a nonsignificant difference between the studied groups regarding resuscitation. ABO was the most common cause of jaundice in the cases [Table 1].
Table 1: Neonatal history of the studied groups

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Treatment modalities of cases

Phototherapy was the most common treatment adopted for jaundice. Triple phototherapy was performed in 76.7% of cases [Table 2].
Table 2: Treatment modalities of cases

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Laboratory investigations of cases before and after phototherapy

There was a highly significant difference between cases regarding total serum bilirubin (TSB) (mg/dl), direct bilirubin (mg/dl), indirect bilirubin (mg/dl), and eosinophil count (/mm3) before and after phototherapy.

There was a nonsignificant difference between the cases regarding hemoglobin level before and after phototherapy [Table 3].
Table 3: Laboratory investigations of cases before and after phototherapy

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Correlation between total bilirubin and eosinophil before phototherapy

There was a negative correlation between total bilirubin and eosinophil before phototherapy (P = 0.011, significant) [Table 4].
Table 4: Correlation between total bilirubin and eosinophil before and after phototherapy

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Correlation between total bilirubin and eosinophil after phototherapy

There was a positive correlation between total bilirubin and eosinophil after phototherapy (P = 0.037, significant) [Table 5].
Table 5: Correlation between total bilirubin and eosinophil after phototherapy

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  Discussion Top


Neonatal indirect hyperbilirubinemia is associated with a variety of conditions. Physiological aspects that contribute to indirect hyperbilirubinemia include increased bilirubin production, less efficient hepatic conjugation, and enhanced bilirubin absorption by the enterohepatic circulation[12].

Most cases of hemolytic disease in the newborn are caused by ABO incompatibility or Rh incompatibility[13].

This study aimed to investigate the effect of phototherapy on peripheral eosinophil counts in newborns with severe indirect hyperbilirubinemia needing phototherapy.

This study was conducted on 30 neonates with indirect hyperbilirubinemia who were recruited from the neonatal ICU at Menouf Hospital and 30 healthy neonates who were enrolled as the control group.

The incidence of physiological jaundice in our study was 13.3%. This coincided with the finding of Pramanik et al.[14], who observed physiological jaundice in 26.7% of the studied cases. The lower incidence in our study was because we included only jaundiced neonates.

The incidence of Rh incompatibility in our study was 20%. There was a higher frequency of ABO incompatibility (66.7%) compared with Rh incompatibility (20%) in our study. Rasu et al.[15] and Moerschel et al.[16] also found that ABO incompatibility was more prevalent than Rh incompatibility in their studies, because of anti-D immunoglobulin administration (Waheed et al.)[17].

Sameer and Giroux[18] reported that neonatal jaundice can be treated in several ways, including phototherapy, exchange transfusion, through breast milk substitute, and through drugs (e.g., intravenous immunoglobulin and phenobarbital).

Phototherapy is a noninvasive modality that has been used for the treatment of neonatal jaundice for more than half a century. Its efficiency in decreasing plasma bilirubin concentration is well documented (Sameer and giroux et al.)[18],[19].

In our study phototherapy was the most common treatment modality used (100%), followed by exchange transfusion in combination with phototherapy (10%) and lastly intravenous immunoglobulin in combination with phototherapy (6.7%).

Xiong et al.[20] found that aggressive use of phototherapy may have increased the mortality among infants weighing 501–750 g. These findings have drawn the attention of pediatricians to the potential side effects of neonatal phototherapy. This was in agreement with Karakakcu et al.[21], who reported that, although phototherapy is the standard treatment for neonatal jaundice, it may lead to potential side effects such as retinal degeneration, diarrhea, dehydration, and skin rash.

In our study, increasing level of eosinophils in blood was assessed as a complication of phototherapy in newborns managed for neonatal indirect hyperbilirubinemia. Before phototherapy, there was a nonsignificant difference between serum eosinophil level in cases and controls. But after treatment with phototherapy for 48–72 h, there was a highly significant difference between serum eosinophil level before and that after exposure to phototherapy (P = 0.001).

Also in our study there was highly significant difference between TSB, direct bilirubin, and indirect bilirubin in case group with P value was 0.001 for each regarding to hemoglobin level before and after phototherapy there was no significant difference in case group (P = 1.92).

In the current study, there was a negative correlation between TSB and blood eosinophil level before phototherapy (r = −0.460, P = 0.011).

This came in agreement with Aydin et al.[22], who showed that there was a negative correlation between TSB and blood eosinophil level before phototherapy (r = −0.12, P = 0.03) in severe indirect hyperbilirubinemic patients.

In our study, there was a positive correlation between TSB and blood eosinophil level after phototherapy (r = 0.382, P = 0.037).

This also came in agreement with Aydin et al.[22], who showed that there was a positive correlation between TSB and blood eosinophil level after phototherapy (r = 0.15, P = 0.02).


  Conclusion Top


Peripheral eosinophil count may be affected by phototherapy. The exact mechanism of neonatal jaundice/phototherapy and later risk of developing asthma is not clear yet, and further prospective studies in larger groups are needed.

Neonatologists should concentrate on underlying problems, as eosinophilia is sometimes clinically insignificant with regard to morbidity and requires no specific treatment. In fact, it may be indirect evidence of clinical recovery. Unless eosinophilia is associated with clinical symptomatology, medical evaluation should be limited to routine follow-up examinations and repeat monitoring of absolute eosinophil counts.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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American Academy of Pediatrics. Management of hyperbilirubinemia in healthy term newborn. Pediatrics 2004; 94:558–565.  Back to cited text no. 1
    
2.
Stocker R, Yamamoto Y, McDonagh AF. Bilirubin is an antioxidant of possible physiological importance. Science 1987; 235:1043–1046.  Back to cited text no. 2
    
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Khan NM, Poduval TB. Immunomodulatory and immunotoxic effects of bilirubin: molecular mechanism. J Leukoc Biol 2011; 90:997–1015.  Back to cited text no. 3
    
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Matheny HE, Deem TL, Cook-Mills JM. Lymphocyte migration through monolayers of endothelial cell lines involves VCAM-1 signaling via endothelial cell NADPH oxidase. J Immunol 2000; 164:6550–6559.  Back to cited text no. 4
    
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Ueki S, Kihara J, Kato H. Soluble vascular cell adhesion molecule-1 induces human eosinophil migration. Allergy 2009; 64:718–724.  Back to cited text no. 5
    
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Keshavan P, Deem TL, Schwemberger SJ. Unconjugated bilirubin inhibits VCAM-1-mediated transendothelial leukocyte migration. J Immunol 2005; 174:3709–3718.  Back to cited text no. 6
    
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Kirk JM. Neonatal jaundice: a critical review of the role and practice of bilirubin analysis. Ann Clin Biochem 2008; 45:452–462.  Back to cited text no. 7
    
8.
Xiong T, Tang J, Mu DZ. Side effects of phototherapy for neonatal hyperbilirubinemia. Zhongguo Dang Dai Er Ke Za Zhi 2012; 14:396–400.  Back to cited text no. 8
    
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Houghton Mifflin Harcourt. Granulocyte. New world medical dictionary. 3rd ed. UK: Houghton Mifflin Harcourt; 2009: 181.  Back to cited text no. 9
    
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Ballard JL, Khoury JC, Wedig K. New Ballard Score, expanded to include extremely premature infants. J Pediatr 1991; 119:417–423.  Back to cited text no. 11
    
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Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. New Engl J Med 2001; 344:581–590.  Back to cited text no. 12
    
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American Academy of Pediatrics Practice Parameter. Management of hyperbilirubinemia in the healthy term newborn. Pediatrics 1994; 94: 558–65.  Back to cited text no. 13
    
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Pramanik T, Pramanik S. Distribution of ABO and Rh blood groups in Nepalese medical students: a report. East Mediterr Health J 2000; 6:156–158.  Back to cited text no. 14
    
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Rasul CH, Hasan MA, Yasmin F. Outcome of neonatal hyperbilirubinemia in a Tertiary Care Hospital in Bangladesh. Malaysian J Med Sci 2010; 17:40–44.  Back to cited text no. 15
    
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Moerschel SK, Cianciaruso LB, Tracy LR. A practical approach to neonatal jaundice. Am Fam Phys 2008; 77:1255–1262.  Back to cited text no. 16
    
17.
Waheed I, Chishti AL, Alvi A, Iqbal A. Hemolytic disease of newborn: can we meet this challenge? Pak Paediatr J 2005; 29:129–132.  Back to cited text no. 17
    
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Sameer Wagle S, Gruslin-giroux A, PG Desphande. Hemolytic disease of newborn. Pediatr Res 2006; 22:188–195.  Back to cited text no. 18
    
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Erlandsen MA, Ruud Hansen TW. Treatment of neonatal jaundice – more than phototherapy and exchange transfusions. East J Med 2010; 15175–185.  Back to cited text no. 19
    
20.
Xiong T, Qu Y, Cambier S, Mu D. The side effects of phototherapy for neonatal jaundice: what do we know? What should we do?. Eur J Pediatr 2011; 170:1247–1255.  Back to cited text no. 20
    
21.
Karakakcu C, Ustdal M, Ozturk A. Assessment of DNA damage and plasma catalase activity in healthy term hyperbilirubenemic infant receiving phototherapy. Mutat Res 2009; 680:12–16.  Back to cited text no. 21
    
22.
Aydin B, Beken S, Zencirogly A, Dilli D, Okumuş N, Blood eosinophil levels in newborns with severe indirect hyperbilirubinemia treated with phototherapy. Iran J Pediatr 2014; 24:267–272.  Back to cited text no. 22
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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