The relation between neonatal phototherapy and
childhood asthma
Heidarzadeh Arani M,Mosaiebi Z , Movahedian AH, Aabedi AR
Assistant professor in asthma and allergy, Kashan University of medical science, Iran
Associate professor in neonatology, Kashan University of medical science, Iran
Associate professor in pediatric cardiology, Kashan University of medical science, Iran
Resident of pediatrics, Kashan University of medical science, Iran
ABSTRACT
Introduction:
Asthma is the most common chronic disease in childhood. Many parameters have known as its
risk factors. Recently, phototherapy have recognized as one of the risk factors for involving in
childhood asthma. Thus, current study has been carried out to identify the relation between
neonatal phototherapy and childhood asthma.
Methods & Materials:
This is an analytical case-controlled study carried out on children involved in asthma with history
of neonatal icter as case group; and children not involved in asthma with history of neonatal icter
as control group (after matching upon age, gender, rout of delivery, and birth weight). Among
400 children been studied, 28 subjects in case group and 34 subjects in control group had
inclusion criteria. The subjects, in case and control groups, have compared upon undergoing
phototherapy and then duration of phototherapy, if they had underwent. Statistical analyzing has
done through Chi-square and T-test statistical methods.
Findings:
Among the children, 26 subjects in case group (92.8%) and 20 subjects in control group (58.8%)
had history of phototherapy (P-value=0.002). Mean numbers of undergoing neonatal
phototherapy in case group were 4.9 and in control group were 3.2 days (P-value<0.0001).
Conclusion:
Neonatal phototherapy is one of the factors affecting on and its duration play a role in involving
with childhood asthma. Therefore it is necessary to take the children under phototherapy only in
specific cases and also with the least duration.
Keywords:
Icter; Phototherapy; Childhood Asthma.
Introduction:
Asthma is the most common chronic childhood disease and has involved five million
under 18 children in US (1, 2). Regarding to existed records, the disease prevalence and
severity increased last years (3, 4). So, identifying its epidemiologic aspects is one of the
most important taxes of health system.
One out of 13 school age children is involved in asthma. The disease accounts as one the
most important causes of physician’s office and emergency rooms referrals,
hospitalizations, and also school absences. From 1893 to 1980, the deaths rate due to
asthma has been duplicated; resulted in 5500 deaths per year. Many various perinatal
factors such as rout of delivery, maternal diseases, birth weight and low gestational age,
have suggested relating with asthma incidence (1).
Recently, phototherapy have recognized as one of the risk factors for involving in childhood
asthma (5). Approximately 60% of term and 80% of preterm neonates experience neonatal icter
during first week of life. Phototherapy or blood exchange used to cure the icter. Various
complications such as dehydration, diarrhea, rashes and deterioration of vitamins (e.g.
Riboflavin) have reported following phototherapy (1).
In a study taken place in Sweden (2007), researchers have found a direct correlation between
neonatal icter and following phototherapy with childhood asthma (5). Through another study in
Japan authors suggested that icter plays a role in alleviating asthma symptoms (6).
Phototherapy influences the neonate immune system by effecting directly on T lymphocytes and
consequently may result in immune system development disturbance during long time. In theory,
inhibition of T lymphocytes function at the time of immune system development during neonatal
period may lead to decrease T helper 2 (Th2) to T helper 1 (Th1) lymphocytes transformation and
then to increase the childhood asthma involving risk (7).
As neonatal phototherapy have been suggested among the risk factors in asthma incidence and
regarding to the paradoxes existed and limited data on neonatal icter and childhood asthma in Iran
and other countries, the current study has been planned to identify the relation between neonatal
phototherapy and childhood asthma in Kashan.
Methods & Materials:
This is an analytical case-controlled study carried out on 28 children with asthma as case group
and 34 children without asthma as control group. Diagnostic criteria for childhood asthma have
based on clinical manifestations such as dyspnea, cough, and wheezing along with spirometery
(in children older than 5) results been carried out by pediatric asthma and allergy specialist. The
subjects have chosen among 200 children referred to asthma and allergy clinic, Shahid Beheshti
hospital, Kashan. Thirty four children without asthma, control group, have chosen randomly
among pediatric ward hospitalized children after complete group matching with case group.
Inclusion criteria included history of neonatal icter in both groups, age of more than 2 and less
than 12 in both groups, lack of current involving in asthma in control group, lack of asthma
history, lack of any chronic respiratory diseases history in control group, and lack of involving in
atopia in both groups.
Patient without mentioned criteria excluded the study. Regarding to higher prevalence of icter in
boys than girls, children in both group have matched upon age and sex; and also upon Sherif et.al.
(10), Kiechl-Kohlendorfer et.al. (11) and Sears et.al. (13), some other risk factors for childhood
asthma included rout of delivery (Caesarian section method), nutrition (powder milk), and birth
weight (low birth weight). Therefore, in order to distinguish the effect of under studied risk
factor, phototherapy, well; all children in both groups have matched upon these factors, too.
Meanwhile, because neonates had very high bilirubine serum level, in order to prevent the
complications (e.g. Kernicterus) they have underwent blood exchange immediately, their
bilirubin serum level have fallen down faster, and may take shorter period of phototherapy ; thus
neonates with history of blood exchange have excluded the study. Also, regarding to the study
Feyzullah et.al.(14) carried out on sepsis role in preventing childhood asthma, children with
history of hospitalization due to any reason but icter have excluded the study.
All the data have gathered from patients by means of holistic questionnaire edited upon research
variables. Patient information extracted from data sheets, have been analyzed using appropriate
abundance tables upon study variables. Gathering the data, they have been analyzed by means of
SPSS#13 software along with Kolmogrov-Smirnov test, T test, Leven test, and Chi-Square.
Findings:
The current study carried out on 28 children in case group and 34 children in control group. In
case group 57.1% and in control group 55.9% of subjects were male, the difference was not
significant (P-value=0.563). In case group 46.4% and in control group 41.2% of subjects have
born through Caesarian section method, the difference was not significant (P-value=0.798). Also
10.7% of case group and 11.8% of control group were Low Birth Weight (LBW), the difference
was not significant (P-value=0.61). No significant difference in age has found between two
groups (P-value=0.99). (See table 1)
In case group 92.8% and in control group 58.8% of children had received phototherapy before,
the difference was significant (P-value=0.002). (Table 2)
Mean duration of neonatal phototherapy were 4.9 and 3.2 days in case and control group (In
subjects with history of phototherapy), respectively; the difference was statistically significant (Pvalue<0.001). (Table 3)
Conclusion:
Asthma is one of the most prevalent diseases whole around the world, its prevalence is
increasing. Although genetic factors play the most important role in asthma, but the current
increasing prevalence during last two decades could not been interpret only with genetic changes
(1). Upon the last studies various factors, such as perinatal ones, play roles in triggering
childhood asthma.
Sherriff et.al.(2001) in Austria, suggested that risk factors of childhood asthma include: male
gender, birth date from April to December, Caesarian section rout of delivery, low maternal age,
consuming powder milk (supplementary milk) (8). Kiechl-Kohlendorfer et.al.(2000-2005) have
evaluated 305 asthmatic children in Australia. In this study asthma risk factors found as male
gender, civilization, history of neonatal hospitalization, lack of breast feeding, parent smoking
after child born, and low birth weight (9).
Sears et.al.(1996) in Canada, concluded that risk factors of asthma in childhood include: male
gender, positive family history, and maternal smoking (10).
Recently, relation of phototherapy and involving in asthma has been mentioned. Nowadays
phototherapy is used vastly in curing mild to moderate neonatal icter. Acute complications of
phototherapy include diarrhea, skin rashes, electrolytes disturbance, and dehydration. Also
phototherapy can lead to deterioration of some vitamins such as Riboflavin, have seen in iceric
children underwent phototherapy (1). Phototherapy has also some long term complications such
as DNA fraction and mutation, have been found in some studies (14). Other hazards and
complications of phototherapy include potential and long term effects on endocrine system,
sexual puberty and DNA repairing mechanisms in epidermis cells (9). On the other hand,
phototherapy affects neonate immune system through direct influence on T lymphocytes; and
consequently can lead to immune system development disturbances. In theory, inhibition of T
lymphocytes function at the time of immune system development during neonatal period may
lead to decrease Th2 to Th1 lymphocytes transformation and then to increase the childhood
asthma involving risks (7).
In studies carried out in Sweden and other European countries, it has conclude that birth time
events, such as phototherapy, result in increasing involvement with autoimmune diabetes (11,
12); so the other theory introduced asthma as autoimmune disease is contribution of asthma and
autoimmune diseases (13).
In current study it concluded that history of phototherapy due to neonatal icter is more frequent in
asthmatic children compared with control group (92.8% in front of 58.8%, P-value=0.002). Also
mean duration of neonatal phototherapy in asthmatic children with history of phototherapy was
more than control group (4.9 in front of 3.2 days, P-value<0.001).
Therefore, regarding achieved findings, it seems that phototherapy can correlate with childhood
asthma.
Related studies are so limited; only Aspberg et.al.(2007) in Sweden, pointed the direct correlation
between neonatal phototherapy and childhood asthma (5). Thus, further studies sound necessary.
In above mentioned study effective factor on childhood asthma has not been distinguish between
neonatal icter and phototherapy, because icter and phototherapy prevalence among asthmatic
subjects in case group was higher than control group; and it is not clear whether neonatal icter
leads to childhood asthma or phototherapy?
But in current study, regarding positive history of icter in both groups, phototherapy has been
established as effective factor in childhood asthma. At the other hand, case group children have
undertaken longer duration of phototherapy with (P-value<0.001). Conclusively, regarding that
phototherapy and its duration in case group were significantly more than control group in current
study, thus it was not clear whether phototherapy is the effective factor on childhood asthma or
its duration ? Therefore, newer and further studies sound necessary.
Many studies suggest that when bilirubin serum level is high enough, phototherapy is effective;
and if bilirubin serum level was low, it just may lead to elongation of treatment duration. On the
other hand, in recent years it has been cleared that bilirubin has beneficial antioxidant traits in
neonates threatened to oxygen toxicity; and has protective role against diseases triggered due to
oxidant factors such as chronic lung disease in premature neonates (BPD), Retinopathy of
premature neonates (ROP), Intra ventricular hemorrhage (IVH), and Periventricular leucomalecia
(PVL) (15-18).
Therefore, upon current and recent studies conclusions, through lack of decreasing and aggressive
treatment of high bilirubin serum level in non-hazardous levels, it is possible to prevent acute and
long term complications (e.g. asthma) and also to benefit from antioxidant traits of bilirubin in
diseases induced with oxidant factors; appropriate solution to decrease the phototherapy duration
has to be identified, too.
Discussion:
Phototherapy is one of the effective factors on childhood asthma and its duration has a role in
involving with childhood asthma, too. It is necessary to take phototherapy just in obligatory cases
with as short as possible duration.
References:
1) Robert M, Waldo E .Nelson Essentials of pediatrice.5th ed,2006:417-430
2) Richard O. Enuresis. In Michael C, Michael A. Oski’s Essential Pediatrics.12th ed.
Lippincott Williams &Wilkins.2004;176(3):487-490
3) Anderson HR. Trends in prevalence and severity of childhood asthma. Brit Med J
1994:1600-1604
4) Senthilselvan A. Prevalence of physician diagnosed asthma in Saskatchewan 1989
to 1990.Chest 1998;(114):388-392
5) Aspberg S, Dahlquist G, Kahan T, Källén B. Is neonatal phototherapy associated
with an increased risk for hospitalized childhood bronchial asthma? Pediatr
Allergy Immunol. 2007 Jun;18(4):313-9. Epub 2007 Mar .
6) Ohrui T, Yasuda H, Yamaya M, Matsui T, Sasaki H. Transient relief of asthma
symptoms during jaundice: a possible beneficial role of bilirubin. Tohoku J Exp
Med. 2003 Mar;199(3):193-6
7) Robert M, Schoenfeld Y. Asthma as a paradigm for autoimmune disease. Int Arch
Allergy Immunol 2003;(132):210-214
8) Sherriff A, Peters TJ, Henderson J, Strachan D. Risk factor associations with
wheezing patterns in children followed longitudinally from birth to 3(1/2) years.
Int J Epidemiol. 2001 Dec;30(6):1473-84.
9) Kiechl-Kohlendorfer U, Horak E, Mueller W, Strobl R, Haberland C, Fink FM, et
al. Neonatal characteristics and risk of atopic asthma in schoolchildren: results
from a large prospective birth-cohort study. Acta Paediatr. 2007;96(11):1606-10.
10) Sears MR, Holdaway MD, Flannery EM, Herbison GP, Silva PA. Parental and
neonatal risk factors for atopy, airway hyper-responsiveness, and asthma. Arch
Dis Child. 1996 Nov;75(5):392-8
11) Rotem M, Schoenfeld Y. Asthma as a paradigm for autoimmune disease. Int
Arch Allergy Immunol 2003;132:210-214
12) Dahilquist G,Kallen B. Indications that phototherapy is a risk factor for insulindepended diabetes. Diabetes Care 2003;26:247-248
13) Hoare C, Wan PO, Williams H. Systematic review of treatment for atopic
eczema. Health Technol Assess 2000;4:88-92
14) Feyzullah C, Hasan S, Asiye N. Effect of neonatal sepsis on the development of
allergies and asthma in later childhood, Int Arch Allergy Immunol 2007;
142:145-150
15) Dani C Martelli E, BertiniG, et al. plasma bilirubin level and oxidative stress in
preterm infants. Arch Dis Child Fetal NeonatalEd.2003;88:F119-123
16) Steven DK, Vreman HJ, Wong RJ, Contag CH. Carbon monoxide and bilirubin
production in neonates. Semin Prenatol.2001;25:85-93
17) Belanger S, Lavoie JC, Chessex P. Influence of bilirubin on the antioxidant
capacity of plasma in newborn infants. Biol Neonate. 1997;71:233-8
18) Dennery PA, McDonagh AF, Spitz DR, Rodgers PA, and Stevenson DK.
Hyperbilirubinemia results in reduced oxidative injury in neonatal Gunn rats
exposed to hyperoxia. Free Radic Biol Med.1995;19:395-404.
Table 1: abundance distribution of under studied children upon demographic variables
Groups
Case
Control
Male
16
19
(%)
(57.1)
(55.9)
Female
12
15
(%)
(42.9)
(44.1)
Normal vaginal delivery
15
20
(%)
(53.6)
(58.8)
Caesarian section
13
14
(%)
(46.4)
(41.2)
Positive
3
4
(%)
(10.7)
(11.8)
Negative
25
30
P-Value
Variable
Gender
0.563
Rout of delivery
LBW
0.798
0.61
(%)
(89.3)
(88.2)
Age (Mean)
6.33
6.34
total
28
34
(%)
(100)
(100)
0.99
-
Table 2: abundance distribution of icteric children upon phototherapy history
Phototherapy
Positive
Negative
Total
(%)
(%)
(%)
26
2
28
(92.8)
(7.2)
(100)
20
14
34
(58.8)
(41.2)
(100)
46
16
62
(74.2)
(25.8)
(100)
history
groups
Case
Control
Total
P-Value
0.002
Table 3: abundance distribution of under studied children upon duration of phototherapy
Phototherapy
duration (days)
Number
Mean
Standard deviation
Statistical analyzez
comparing both
groups
group
Case
26
4.9
1.3
0.001
Control
1.1
3.2
1.1