ospital ng makati department of pediatrics
TRANSCRIPT
Ospital ng Makati Department of Pediatrics
Comparative study of Prototype Low-Cost Light Emitting Diode Phototherapy Device versus
Conventional Fluorescent Phototherapy in the Treatment of Indirect Hyperbilirubinemia
among Term Infants in a Tertiary Government Hospital
Viel M. Bagunu, M.D.
Author
Ma. Lucila M. Perez, MD, MSc, FPPS
Co-author
ABSTRACT
Title: Comparative study of Prototype Low-Cost Light Emitting Diode Phototherapy Device versus Conventional Fluorescent Phototherapy in the Treatment of Indirect
Hyperbilirubinemia among Term Infants in a Tertiary Government Hospital Viel M. Bagunu MD, Ma. Lucila M. Perez, MD
Background:
Rate of decline during phototherapy for hyperbilirubinemia depends on several factors including the type of phototherapy light. Light emitting diodes (LED) are power efficient, low heat producing light sources that have the potential to deliver high intensity light of narrow wavelength band which could result in potentially shorter treatment time. The Ateneo Innovation Center developed a low cost prototype LED phototherapy device for use in hospitals with low resources.
Objective: A collaboration with the Ateneo Innovation Center was done to develop and test
effectiveness of low cost prototype LED phototherapy device.
Methods: A randomized controlled clinical trial on term neonates with indirect hyperbilirubinemia
in Ospital ng Makati from January-December 2017 were randomly assigned to either undergo phototherapy using LED phototherapy device versus Conventional Fluorescent Phototherapy. Levels of bilirubin were determined after 24 and 48 hours of phototherapy. Side effects were also observed.
Results: After 24 hours, adjusted mean bilirubin levels of those who underwent LED
phototherapy was significantly lower as compared to conventional phototherapy (17.27 ± 2.31 mg/dl versus 18.64 ± 2.81 mg/dl, p=0.000). After 48 hours, there was consistently lower bilirubin in the experimental group (13.37 ± 2.213 mg/dl versus 15.4 ± 2.496 mg/dl, p=0.000). There were no reported side effects in both groups.
Conclusion: Both LED and Conventional Phototherapy devices were effective in treating
hyperbilirubinemia in neonates. However, the use of LED phototherapy showed significantly better bilirubin-lowering effect. The use of this device especially in hospitals with scarce resources may be considered.
Keywords: Phototherapy, LED Phototherapy, Bilirubin, Term neonates
INTRODUCTION
Neonatal jaundice refers to yellow discoloration of skin and sclera due to
accumulation of bilirubin in the skin and mucous membranes. It affects 60 % of full-term
infants in the first week of life. 1
Hyperbilirubinemia, defined as an increased level of bilirubin above normal levels, is
one of the most common problem in neonates. Jaundice caused by indirect
hyperbilirubinemia is a frequent cause for admission in health care facilities all around the
world. 1
About 80% of severe cases of indirect neonatal hyperbilirubinemia occurs in
resource-limited settings.2 In addition, an increased incidence in diagnosis of neonatal
jaundice is noted among east Asian and mixed Asian /white infants than those among white
infants have been reported.3
Though a common problem worldwide, indirect hyperbilirubinemia can remain
benign if prompt management is available. Since its introduction since 1958, phototherapy
has remained the cornerstone for the treatment of neonatal hyperbilirubinemia.4
Phototherapy can be delivered using different light sources and different light
alternatives have been considered.5
In recent years, the light emitting diodes (LED), has been studied and shown to be a
good light source alternative for phototherapy. A number of advantages for the LED
technology include: lower energy consumption, longer endurance time of the lamps, infrared-
free and ultraviolet- free radiation, and higher cost efficiency.5
Although phototherapy is proven and cost effective tool to treat hyperbilirubinemia, it
is not accessible to more than 6 million (~45%) of at-risk infants worldwide.1. One of the
reasons for the inaccessibility is the high cost of a single phototherapy unit. A conventional
phototherapy light unit costs an estimated Php100,000 to 200,000, making it inaccessible to
some public hospitals. Though some hospital may be able to procure it, the number of
available units in each hospital may not be able to cater to the number of patients in need of
treatment . Thus multiple patients may have to share a single phototherapy unit and some are
advised to transfer and seek admissions to other hospitals thereby increasing the risk of the
patient not availing the necessary prompt treatment.
This study was done to test a prototype phototherapy device that will be more
accessible to resource-limited settings for public consumption. A collaboration with the
Ateneo Innovation Center was formed to develop and test the effectiveness of a low-cost
prototype LED phototherapy device.
REVIEW OF RELATED LITERATURE
Neonatal hyperbilirubinemia is a common clinical problem encountered during the
neonatal period, especially in the first week of life.3
Unconjugated hyperbilirubinemia in which the direct-reacting bilirubin level is less
than 15 % of serum total bilirubin is the most common form of jaundice seen in newborn
infants. 7 Phototherapy is still the mainstay of treatment of neonatal hyperbilirubinemia.
Phototherapy lamps with output in the blue to green part of the spectrum are most effective in
lowering serum bilirubin levels. At these wavelengths, light penetrates the skin well and is
absorbed strongly by bilirubin. 8
Different skin colors manifest different traits to light exposure. In fact skin color is
primarily determined by melanin that is synthesized in the melanosome. Melanosomes in
dark skin (African) are larger and more heavily pigmented than those in light skins (Asian
and Caucasian). Since melanin can reduce the penetration of light, neonates with black skin
may need more intensive phototherapy. 9
Prototype light-emitting diode (LED) lights have been developed and tested in clinical
and laboratory studies. These are power-efficient, durable light sources that provide high-
intensity light in the blue portion of the visible spectrum. The LEDs emit light through a
narrow wavelength band with a peak emission between 450 and 470nm. 7
In a study conducted by Kumar P. et al, they compared the efficacy of LED
phototherapy to conventional phototherapy such as halogen light sources and compact
fluorescent light sources in decreasing TSB levels and duration of treatment in neonates with
unconjugated hyperbilirubinemia. It was concluded in the study that LED light source
phototherapy is as affective in decreasing TSB at rates that are similar to phototherapy with
conventional light sources. 6
Another study conducted by Maisels et al compared the efficacy of light-emitting
diode (LED) phototherapy with special blue fluorescent tube phototherapy in the treatment of
neonatal hyperbilirubinemia. The study concluded that LED phototherapy is as effective as
special blue fluorescent tube phototherapy in lowering serum bilirubin levels in term and
near-term newborns. The small size, high luminous intensity and narrow wavelength band
light of LED phototherapy makes this a useful method for delivering intensive phototherapy
to newborn infants.10
SIGNIFICANCE OF THE STUDY
Phototherapy is still the recommended standard of treatment of hyperbilirubinemia
but scanty supply of resources in settings with limited access and care may direct the patients
to a higher morbidity and mortality risk. 11
The result of this study can help provide evidence on whether a low-cost LED
phototherapy prototype device is effective in lowering bilirubin as compared to conventional
fluorescent device which can be used in hospitals with scarce resources.
OBJECTIVES
General Objectives: To evaluate the efficacy of a prototype LED phototherapy device
versus conventional fluorescent phototherapy in lowering serum bilirubin levels among term
infants diagnosed with indirect hyperbilirubinemia
Specific Objectives:
1. To determine the decrease in Total Serum Bilirubin during the first 24 hours and 48 hours
under LED versus conventional fluorescent phototherapy presented as:
a. mean difference from baseline
b. % change in bilirubin from baseline
c. rate of decline of baseline serum Total Serum Bilirubin (TSB)
2. To determine the occurrence of treatment failure among term infants under LED
phototherapy device as compared to conventional fluorescent phototherapy
3. To identify possible side effects of using LED phototherapy and conventional fluorescent
phototherapy
METHODOLOGY
STUDY DESIGN:
This is a single-blind randomized controlled clinical trial conducted on term infants
diagnosed with indirect hyperbilirubinemia admitted at the nursery, OB ward, and pediatric
ward of Ospital ng Makati from January-December 2017 that were assigned to undergo
phototherapy using either LED phototherapy device or conventional fluorescent
phototherapy. Levels of bilirubin were determined after 24 and 48 hours of phototherapy.
Side effects were also observed.
INCLUSION/EXCLUSION CRITERIA
Included in this study were healthy, Filipino, term infants, completed 37 to 42 weeks
age of gestation with weights appropriate for gestational age, diagnosed with indirect
hyperbilirubinemia needing phototherapy. The need for phototherapy will be based on the
age of infant (hour of life) and total serum bilirubin levels classified as high risk and high
intermediate risk which is above the 75th percentile based on hour-specific serum bilirubin
nomogram. (APPENDIX D ) but not exceeding a total serum bilirubin level of more than 25
mg/dl. Infants included in the study also had normal physical examination and laboratory
results such as complete blood count, reticulocyte count, and Coomb’s test.
Excluded in the study were subjects who developed jaundice during the first 24 hours
of birth, direct bilirubin levels more than 20 % of total bilirubin, those who need exchange
transfusion at the time of enrollment; with co-morbids such as neonatal sepsis, neonatal
pneumonia, and those with congenital malformations.
SAMPLE SIZE
Subjects were recruited consecutively as they were diagnosed and deemed eligible
based on inclusion/exclusion criteria.
Using the sample size calculator at http://hedwig.mgh.harvard.edu/sample_size, a
total of 46 patients was calculated with the following conditions : power: 80%, level of
significance = 0.05, difference in means = 0.86 based on results of initial 30 subjects of this
study.
INTERVENTION
The study was thoroughly explained to the parents. They were instructed to read and
sign the informed consent prior to enrollment (APPENDIX A)
Clinico-demographic data of all infants recruited and enrolled in the study were
documented in data sheets. These included the weight, age of gestation at birth, age at the
start of phototherapy, feeding history, maternal blood type, patient’s blood type, cause of
hyperbilirubinemia and baseline total serum bilirubin levels. (APPENDIX E)
All infants enrolled who met the eligibility criteria were randomly assigned. Random
assignments were prepared and placed in sealed opaque envelopes which were arranged
sequentially. Enrolled infants were assigned into Group A, the experimental group were
exposed to LED phototherapy (APPENDIX B) and Group B, the control group, who were
exposed to conventional phototherapy (APPENDIX C).
The prototype low cost LED phototherapy unit was custom made in collaboration
with Ateneo Innovation Center . It was made using 20 pieces blue LED lamps connected in
paralleled for a total power rating of 60W. A Spectro-Vis Plus ( Vernier) was used to
determine the spectrum of the LED lamps. The emission spectrum was found to be 462.1-
476.4 nm, which falls within the most effective range (460-490nm ) for phototherapy. The
intensity of the LED lamp was 8.49 w/m2, measured using a light intensity meter. The
calculated value of the irradiance was 54 uW/cm2/nm. This value is almost 2x higher than the
minimum recommended irradiance required for intensive phototherapy at 1m distance. The
total cost for the development of the prototype equipment was approximately Php 20, 000 .
Pilot study was done prior to this randomized controlled trial to test efficacy and safety of
the phototherapy.13
Infants were exposed completely unclothed, with their eyes and genital regions
properly covered, to continuous phototherapy only interrupted during feeding, cleaning,
blood sampling, and turning to sides every 2-3 hours. The interruptions in phototherapy were
monitored and mothers were instructed to write down the number and duration of
interruptions such as breastfeeding, cleaning and blood extractions in a data collection form
that was provided (APPENDIX F).
All enrolled subjects were monitored daily by the nurse-in-charge (APPENDIX G)
including daily weight, temperature every 4 hours and urine output every shift.
Complications such as skin rashes, diarrhea and dehydration were also monitored.
Occurrences of such complications were managed according to the standards of care such as
hydration for diarrhea and hyperthermia, application of therapeutic ointments for rashes or
burns and possible referral to other services such as Dermatology and Surgery, if the need
arose.
All eligible subjects who developed untoward side effects or co-morbidities such as
hospital -acquired infections during the study were withdrawn from the study. Those
subjects exposed to LED phototherapy who after first 24 hours of phototherapy showed an
increase in total serum bilirubin were withdrawn from the study and shifted to conventional
phototherapy. After 48 hours of using LED phototherapy , those subjects who still required
further phototherapy were shifted to conventional phototherapy.
OUTCOMES
Primary outcome results included the average rate of decline of the total serum
bilirubin (TSB) level (mg/dl per hour) during the first 24 hours and 48 hours based from the
baseline bilirubin levels. Secondary outcomes determine the occurrence of treatment failure,
defined as need for blood exchange transfusion or additional phototherapy if with rebound
increase in the TSB levels, and the safety of the device measured by the occurrence of
possible side effects such as skin rash, diarrhea, dehydration, hypothermia and hyperthermia.
Total serum bilirubin levels were obtained through blood extraction using peripheral
venipuncture at baseline then every 24 and 48 hours of phototherapy exposure. . Serum
bilirubin levels were analyzed by blinded medical technologists in the laboratory of the
tertiary government hospital using clinical chemistry analyzer Architect C4000 model by
Abbott.
ANALYSIS
Descriptive statistics such as mean, standard deviation ( SD), frequency and
percentages were used to present the baseline characteristics of the comparison groups. Chi-
square test was used to compare the gender, patient’s blood type, maternal blood type,
diagnosis and method of feeding in both groups. Independent t-test was used to compare
weight ( kg), age of gestation ( weeks), and day of life ( days).
Frequency and percentages were used to report the outcome of patient based on
duration of phototherapy. Z-test of proportion was used to compare the proportion of patients
completed treatment.
The mean bilirubin levels and average rate of decline of the total serum bilirubin level
and duration of phototherapy with + 1 standard deviation were compared. The proportion of
neonates who developed rebound hyperbilirubinemia and complications to phototherapy
intervention were also be compared. In comparing the baseline bilirubin against the 24th and
48th hour bilirubin, paired t-test was used. Since there was noted significant difference in
baseline TSB in comparative groups, ANCOVA ( Analysis of Co-variance ) was employed.
The level of significance was set at 5%.
ETHICAL CONSIDERATION
A voluntary informed consent (APPENIDX A) was obtained from the parents or legal
guardian of the subjects prior to their inclusion in the study. Confidentiality of patients’
information was maintained at all times . Only the investigator and those involved in the data
processing were allowed access to these records. The study protocol was reviewed and
approved by the hospital research and ethics committee. A preliminary study was conducted
first to assess the lowering capacity and safety of the low cost LED phototherapy light prior
to this randomized clinical trial in compliance with the recommendation of the hospital
research and ethics committee. The study showed that the prototype low cost blue LED
phototherapy was able to lower serum bilirubin level among term infants with indirect
hyperbilirubinemia and appeared to be safe to use. 17
Subjects were monitored regularly for occurrence of possible complications such as
skin rashes, temperature instability and dehydration. Those in the LED phototherapy group
whose TSB increased on follow-up were shifted to conventional fluorescent phototherapy to
prevent worsening of jaundice.
RESULTS
Ninety nine (99) patients were recruited and randomly assigned into two groups.
Fifty subjects were assigned in Group A which were exposed to LED phototherapy while
forty -nine, subjects were assigned to Group B under conventional phototherapy.
In both groups, the average age of gestation was 38-39 weeks, with a mean age upon
admission of 5 days, average weight of 3 kg. There were more females enrolled in the LED
group (52.0%) but, more males in Conventional group (55.1%). Most of the patients were
blood type O. Most patients in both groups were diagnosed with breastfeeding jaundice. All
patients were exclusively breastfed.
Table 1. Baseline characteristics of the comparison groups LED phototherapy
N=50 Conventional phototherapy
N=49
P value
Age of Gestation ( weeks ), mean ± 1SD
38.44 ± 1.05 38.53 ± 1.08 0.675 **
Day of life ( days ), mean ± sd 4.58 ±1.37 4.61 ±1.55 0.919 **
Gender, n% 0.548 **
Male 24 (48.0 %) 27 (55.1%) 0.613 **
Female 26 (52.0%) 22 (44.9%) 0.613**
Weight ( kg ), mean ± sd 2.9 ± 0.32 3.0 ±0. 37 0.153 **
** not significant
In terms of feeding interruption, mean duration of breastfeeding, cleaning time,
interruptions of phototherapy (ex. blood extraction) were approximately similar in both
groups. Turning was done every 2-3 hours for all patients. (See Appendix F)
Comparison of Bilirubin Levels
A. Bilirubin Levels
Figure 1 shows that the initial total serum bilirubin (TSB) level of the LED
phototherapy group was significantly higher than among those in the Conventional Group
(mean TSB of 21.2 + 1.9 mg/dl versus 19.8± 2.61 mg/dl, p=0.001). After 48 hours, mean TSB
of those exposed to LED phototherapy were lower as compared to conventional (mean TSB
of 13.68 ± 2.09 mg/dl versus 15.1 ± 2.7 mg/dl, p=0.000)
Patient’s Blood type (n, %) 0.428 **
A 9 (18 %) 9 ( 18.3 %) 0.824 **
B 15 (30 % ) 9 ( 18.3 %) 0.261 **
O 26 (52%) 30 ( 61.2%) 0.471 **
AB 0 (0%) 1 (2%) 0.992 **
Maternal Blood type (n , %) 0.481 **
A 12 (24% ) 8 (16.3%) 0.482 **
B 20 (40%) 16 (32.6 %) 0.578 **
O 17 (34%) 23 (46.9%) 0.270 **
AB 1 (2%) 2 ( 4%) 0.995**
Diagnosis (n, %) 0.678 **
Breastfeeding jaundice 48 (96%) 46 (93.8 %) 0.678 **
ABO incompatibility
OA set-up 1 (2%) 2 (4%) 0.676 **
OB set-up 1 (2%) 1 (2%) 1.000 **
Breastfeeding 50 (100%) 49 (100%) 1.000 **
baseline 24 hours 48 hours LED 21.21217391 17.68897959 13.675625
Conven<onal 19.84511111 18.12270833 15.10163265
0
5
10
15
20
25
Bilirub
in Levels
Mean Bilirubin Levels
Figure 1: Mean TSB levels in both groups at different period of time
B. Comparison within Groups
Table 2 shows that there is a significant difference in the mean bilirubin levels within
each group after 24 and 48 hours. These results demonstrate that both interventions are
significantly effective in treating jaundice for babies with the use of LED showing better
results than the conventional method especially during the 24 to 48 hour window of
treatment.
Table 2. Paired Comparison within groups
Type of Phototherapy
Mean Differenc
e +1 SD P value Conventional Pair 1 TSB* after 24 hours compared to
Baseline TSB -1.80 1.78 .000†ƚ
Pair 2 TSB after 48 hours compared Baseline TSB
-4.86 2.07 .000†ƚ
Pair 3 TSB after 48 hours compared to TSB after 24 hours
-3.05 2.06 .000†ƚ
LED Pair 1 TSB* after 24 hours compared to Baseline TSB
-3.41 1.95 .000†ƚ
Pair 2 TSB after 48 hrous compared Baseline TSB
-7.58 2.76 .000†ƚ
Pair 3 TSB after 48 hours compared TSB after 24 hours
-4.27 2.25 .000†ƚ
*TSB = Total serum bilirubin
† ƚ Significant
C. Comparison between Groups
Table 3 below showed that there was a statistically significant difference in baseline
mean bilirubin between two groups (P=0.11)
LED phototherapy group (mean 21.2 mg/dl + 1.9) was higher than among those in the
Conventional Group (mean 19.8 mg/dl ± 2.61). After 24 and 48 hours, there is noted
statistically significant change in mean bilirubin of those exposed to LED phototherapy (
17.69 mg/dl ± 2.27; 13.68 ± 2.09 13.68; ) as compared to conventional (18.12 mg/dl ± 2/357;
15.1 ± 2.7). Moreover, there is also noted statistically significant change in mean difference
and percentage in both groups ( p=00)
Table 3 . Serum Bilirubin levels between two groups (Unadjusted)
Timing Bilirubin Levels Unadjusted
P value LED Phototherapy (mg/dl, mean ± SD) N= 50
Conventional Phototherapy (mg/dl, mean ± SD) N= 49
Baseline Bilirubin ( mean ± SD)** 21.2 ± 1.9 19.8± 2.61 0.011*
24th Hour** 17.69 ± 2.27 18.12 ± 2.37 0.431
Mean difference from baseline** 3.89 1.87 0.00*
% change from baseline 15.37 ± 8.26 7.8 ±7.60 0.00*
48th Hour of life** 13.68 ± 2.09 15.1 ± 2.70 0.004*
Mean difference from 24th Hour** 4.26 3.06 0.007*
% change from 24th Hour 23.71 ± 12.03 14.45 ± 10.18 0.007 *
Mean difference 48 hours to baseline** 7.23 ± 2.79 5.15 ± 2.36 0.00*
% change from 48 hours to baseline** 35.3 +/- 13.06 23.16 +/- 10.90 0.00 *
*Significant
Since comparison of the baseline TSB levels of the two groups were shown to be
statistically different, adjustments were made for the covariate of baseline bilirubin levels.
The adjusted means showed that patients exposed to LED photolight had significantly lower
levels of bilirubin compared to those exposed in conventional methods at 24 hours (p=0.000)
and 48 hours of treatment (p=0.000), respectively. The rate of decline is significantly
different in LED group at 0.16 ± 0.146069 mg/dl/hour (p=0.000), versus Conventional
group at 0.09 ± 0.10742 (p=0.000)
Table 4. Comparison of Serum Bilirubin levels between two groups
Timing Bilirubin Levels Adjusted**
P value
LED Phototherapy (mg/dl, mean ± SD) N= 50
Conventional Phototherapy (mg/dl, mean ± SD) N= 49
24th Hour** 17.270 ± 2.31 18.640 ± 2.81 0.000*
48th Hour** 13.37 ± 2.213 15.4 ± 2.496 0.000*
*significant **ANCOVA Table 5 showed that after 24 hours of phototherapy under LED, 4% of the
patient completed treatment as they are classified under low risk zone, while none completed
treatment under convetional phototherapy. Furthermore 86 % of the patient completed
treatment after 48 hours under LED phototherpay while only 59% were observed under
conventional. However, 1% of the subjects under LED phototherapy while 41% of subjects
under conventional still needed further treatment after 48 hours . All subjects who completed
phototherapy were all discharged in stable condition.
There was no significant difference in the proportion of neonates who
completed treatment between LED phototherapy and conventional phototherapy after 24
hours of treatment (p=0.484). However, by 48 hours, a significantly higher percentage
of those in the LED group had completed treatment as compared to the Conventional
phototherapy group (86% versus 59%, respectively, p=0.05). In the LED group, only 1% of
the neonates needed to continue phototherapy.
* significant
Complications
None of the subjects experienced complications while on phototherapy treatment
such as skin rashes, hypothermia nor hyperthermia. All subjects had an adequate urine
output . Results showed that mean urine output for those exposed to LED phototherapy was
5. 0 cc/kg/hour, while on conventional phototherapy was 5. 2 cc/kg/hour
Table 5 Comparison of Outcome between two groups P value
LED Phototherapy N=50
Conventional Phototherapy
N= 49
Completed treatment after 24 hours (n, % )
2 ( 4.0%) 0 0.484
Completed treatment after 48 hours (n, % )
43 (86.0 %) 29 (59 %) 0.005*
Continued treatment after 48 hours (n, % )
5 (1.0%) 20 (41%) 0.000*
DISCUSSION
This randomized study showed that both the prototype LED and Conventional
Phototherapy devices were effective in treating hyperbilirubinemia in neonates. However,
the use of LED phototherapy showed significant better serum bilirubin-lowering effect.
A meta-analysis in 2011 on the efficacy of LED phototherapy on hyperbilirubinemia
concluded that there is no significant difference in TSB rate of decrease between LED and
other types of phototherapy although three of the five populations included in the meta-
analysis gave a rate of decrease of TSB in favor of LED phototherapy without reaching
statistical significance12, 6
In addition, Majid Mohammadizadeh et al. (2012) also showed that LED light source
is as effective as fluorescent tubes for the phototherapy of preterm infants with indirect
hyperbilirubinemia.13
However, concurring study in 2018 showed significant reduction of exposure in
LED 50.18 ±6.7 hrs versus Conventional 65±13.7 hrs (p<0.05). It also showed that there is a
significant reduction of TSB level in LEDs more than the conventional. 14
Another study by Karagol (2006), LED phototherapy was found to be more efficient
than conventional phototherapy as they can provide more bilirubin photodegradation, which
coincide with the results of the study. This finding was confirmed by more recent studies. 15
Junaid, Ahmed et al. (2018), compared LEDs with fluorescent phototherapy units in
the treatment of neonatal jaundice and the results showed significant fall in greater decrease
in rate of TSB in LED at 0.45 mg/dl/hour (p=0.472) and 0.10 mg/dl/hour in florescent
phototherapy (p=0.472) . However, in this study, the drop rate of TSB in LED was also
noted at 0.16 mg/dl/hour which significantly lesser ( p=0.000) and 0.9 mg/dl/hour in
conventional therapy respectively which is not significant. This dissimilarity maybe due to
difference the difference in profile of the patient based on entry criteria ( term versus
preterm), sample size, phototherapy devices used. Moreover, there was noted shorter mean
duration of phototherapy in LED versus conventional at 48.1 ± 24.1 hours and 96.3 ± 33.2
hours, which is parallel to the results of this study wherein 99% of patient under LED
phototherapy completed treatment after 48 hours.16
A pilot study was conducted on the prototype LED phototherapy among healthy term
infants with jaundice to check the safety and bilirubin-lowering effect of the devise prior to a
full blown randomized controlled trial.
The results presented in an unpublished local study by Calabia, VM (2017)17
showed that the LED phototherapy prototype device was able to demonstrate lowering of
serum bilirubin among term infants and appeared safe to use. Our results are consistent with
the pilot study wherein no complications was noted and a significant decrease in levels of
TSB was recorded. However, in the pilot study, irradiance was noted at 84 uW/cm2/nm but
on the present irradiance of phototherapy decline to 59.40 uW/cm2/nm which is still
acceptable irradiance for standard phototherapy . One of the major, often unrecognized factor
for the decline in irradiance is the hours of use of the phototherapy light. In both LED and
fluorescent bulbs, hours of use is indirectly related to level of irradiance. 17
Complications associated with phototherapy include skin rashes, dehydration, and
temperature instability. None of these were observed among subjects in this study maybe
because they are placed in a controlled environment and regular monitoring of vital signs
were done. In Yurdadok ( 2015)18 report, LED with high irradiance (60-120 uW/cm2/nm)
significantly increases body temperature compared to infants under conventional
phototherapy (10-15 uW/cm2/nm) or LED phototherapy (26-60 uW/cm2/nm). Thus, the
increase in body temperature is a function of increase of irradiance rather than the type of
light source. In this study, tempature instability such as hyperthermia and hypothermia were
not observed among subjects exposed to LED prototype that emits 59.40 uW/cm2/nm and
the conventional phototherapy that emits 15 uW/cm2/nm.
The results of the study maybe use as a point of reference for further development and
technological advancement of the prototype LED. Further studies using the prototype LED
phototherapy in larger scale, jaundiced neonates with sepsis, hemolytic and non-hemolytic
jaundice and comparative study on the efficacy of prototype LED phototherapy in Filipino
term and preterm infants can be explored.
Limitation of the study is the blinding, wherein single-blind controlled clinical trial
was employed. Only the medical technologist who run the tests were blinded. The
investigator and the parents could not be blinded because the phototherapy devices were
easily differentiated. Another limitation observed in the study is the baseline mean serum
bilirubin wherefore baseline mean TSB was higher in the LED group. These study results are
also limited to term babies with no evidence of infection based on the eligibility criteria of
the study.
CONCLUSION / RECOMMENDATION
In this study, both the low-cost LED prototype and Conventional Phototherapy
devices were effective in treating hyperbilirubinemia in neonates. However, the use of the
prototype LED phototherapy showed significantly better bilirubin-lowering effect. Thus, the
use of this device especially in hospitals with scarce resources may be considered. Further
studies that compares the efficacy of prototype LED phototherapy in Filipino preterm infants
can be ventured on.
REFERENCES
1. Thielemans L, Trip-Hoving M, Landier J, Turner C, Prins TJ, Wouda EMN, et al. Indirect neonatal hyperbilirubinemia in hospitalized neonates on the Thai-Myanmar border: a review of neonatal medical records from 2009 to 2014. BMC Pediatr. 2018 Jun 12;18(1):190. PMID: 29895274
2. Maisel, MJ. Neonatal Jaundice. Pediatrics in Review. Dec 2006. 27(12): 443-453
3. American Academy of Pediatrics Subcommitee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics.2004; 114 (1) 297-316
4. Setia S, Villaveces A, Dhillon P, Mueller BA. Neonatal jaundice in Asian, white, and
mixed-race infants. Arch Pediatr Adolesc Med. 2002 Mar;156(3):276-9. PMID: 11876673
5. Vreman HJ, Wong RJ, Stevenson DK. Phototherapy: current methods and future directions. Semin Perinatol. 2004 Oct;28(5):326-33. Review. PMID: 15686263
6. Kumar P, Chawla D, Deodari A. Light-emitting diode phototherapy for unconjugated hyperbilirubinaemia in neonates. Kumar P, Chawla D, Deorari A. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD007969. doi: 10.1002/14651858.CD007969.pub2. Review. PMID: 22161417
7. Colindres JV, Rountree C, Destarac MA, Cui Y, Pérez Valdez M, Herrera Castellanos M, Mirabal Y, Spiegel G, Richards-Kortum R, Oden M. Prospective Randomized Controlled Study Comparing Low-‐Cost LED and Conventional Phototherapy for Treatment of Neonatal Hyperbilirubinemia. J Trop Pediatr. 2012 Jun;58(3):178-83. doi: 10.1093/tropej/fmr063. Epub 2011 Sep 13. PMID: 21914717
8. Ennever, JF. Blue light, green light, white light, more light: treatment of neonatal jaundice. Clin Perinatol. 1990
9. Tao Xiong, Yi Qu., Stephanie Cambier, Dezhi Mu. The side effects of phototherapy for neonatal jaundice: what do we know? What should we do? Eur J Pediatr (2011) 170:1247–1255
10. Maisels MJ, Kring EA, DeRidder J. Randomized controlled trial of light-emitting diode phototherapy. J Perinatol. 2007 Sep;27(9):565-7. Epub 2007 Jun 28. PMID: 17597827
11. Harsha L, Priya J, Shah K, Reshmi B. Systemic Approach to Management of Neonatal jaundice and prevention of kernicterus. Research Journal of Pharmacy and Technology.2015; 8(8)
12. Tridente A, De Luca D. Efficacy of light-emitting diode versus other light sources for treatment of neonatal hyperbilirubinemia: a systematic review and meta-analysis. Acta Paediatr. 2012 May; Epub 2012 Jan 9. Review. PMID: 22168543
13. Mohammadizadeh M, Eliadarani FK, Badiei Z. Is the light-emitting diode a better light source than fluorescent tube for phototherapy of neonatal jaundice in preterm infants? Adv Biomed Res. 2012;:51. doi:. Epub 2012 Aug 28. PMID: 23326782
14. Hamidi, M ; Aliakbari, F. Comparison of Phototherapy with light-editing diodes (LED) and Conventional Phototherapy (fluorescent lamps) in Reducing Jaundice in Term and Preterm Newborns . World Family Medicine. 2018
15. Karagol BS, Erdeve O, Atasay B, Arsan S. Efficacy of light-emitting diode phototherapy in comparison to conventional phototherapy in neonatal jaundice. Journal of Ankara University, Faculty of Medicine. 2007
16. Junaid Ahmed, Komal Atta, , Sadia Zafar, Gul Afshan. Comparison of LED phototherapy with conventional phototherapy in the treatment of hyperbilirubinemia in neonates in terms of safety and effectiveness. JUMDC. Jan-Marc 2018
17. Calabia, VM, Perez MA. Bilirubin lowering effect and safety of prototype low-cost blue light emitting Diode (LED) phototherapy device in the treatment of indirect hyperbilirubinemia among healthy term infants in a tertiary government hospital. Ospital ng Makati. Unpublished. 2017
18. Yurdakok M. Phototherapy in the newborn: what’s new? Journal of Pediatric and Neonatal Individual Med, 2015. 4(2) e040255
APPENDICES
APPENDIX A
Consent Form
Title: Comparative study of light emitting diode (LED) photherapy device vs conventional flourescent phototherapy in treatment of indirect hyperbilirubinemia among health term infants in Ospital ng Makati
Ang katibayang ito ay nagbibigay ng impormasyon ukol sa pagsusuring medikal. Sa
oras na maunawaan ko ang nilalaman nito, ako ay hihingan ng lagda kung pahihintulutan
kong mailahok and aking anak. Nauunawan ko na gagawa ng pagsusuri ukol sa mabuting
idudulot ng paggamit ng LED phototherapy unit sa paglunas ng paninilaw ng aking anak.
Ipinaliwanag sa akin na ang mga ilalahok sa pag-aaral na ito ay yaong mga sanggol
na ipinanganak na husto sa buwan at walang ibang karamdaman maliban sa pagkakaroon
ng mataas ng lebel ng bilirubin na nagiging sanhi ng kanilang paninilaw. Ipinaliwanag sa
akin na ang LED phototherapy na gagamitin ay nabuo sa tulong ng Ateneo Innovation
Center, na ito ay naiiba sa karaniwang ginagamit ng ospital na conventional phototherapy
gamit ang fluorescent light. Naintindihan ko na layunin ng pag-aaral na ito na subukin ang
kakayahan ng LED phototherapy upang mapababa ang lebel ng bilirubin ng aking anak.
Aking nauunawaan na sa pamamagitan ng paglahok ng aking anak sa pagsusuri, ito ay
maaring makadagdag ng kaalaman sa makasiyensyang pamamaraan ng pagpapabilis ng
pagbaba ng paninilaw ng mga sanggol.
Naipaliwanag po sa akin na kukuhanan ng dugo ang aking anak bago magsimula ang
pagpapailaw, sa ika 24 at 48 na oras ng pagpapailaw. Naipaliwanag din po sa akin at aking
naintihdihan na kakailanganing pailawan ang aking anak sa ilalim ng LED phototherapy ng
tuloy-tuloy at magagambala lamang ito sa tuwing kailangan nyang dumede, linisan at
kuhanan ng dugo. Ipinaliwanag din na kapag bumaba na ang lebel ng bilirubin ng aking
anak matapos ang 48 hours na pagpapailaw sa ilalim ng LED phototherapy ay isasailalim na
siya sa pagpapailaw gamit ang kombensyonal na phototherapy na fluorescent hanggang sa
maging normal ang lebel ng kanyang bilirubin. Sa aking pagpayag na ilahok ang aking anak
sa pag-aaral na ito ay nauunawaan ko rin ang aking papel na gagampanan na sagutan ang
monitoring sheet kung saan aking itatala ang oras kung kailanmagagambala ang
pagpapailaw sa kanya sa ilalim ng LED phototherapy tulad ng oras ng pagpapadede,
pagpapaligo at pagkuha sa kanya upang kuhanan ng dugo.
Naunawaan ko na posibleng magkaroon ng mga di inaasahang reaskyon sa bata
katulad ng pamumula ng balat o pagkakaroon ng rashes, pagtatae, paglalagnat, pagkatuyot
o dehydration. Ganunpaman, naunawaan ko na may masinsinang pagbabantay na gagawin
upang maiwasan ang mga posibleng komplikasyon na nabanggit. Kung magkakaroon man
ng anumang reaksyon dulot ng pagsusuring ito ay alam ko na bibigyan ito ng kaukulang
paglunas ng mga doktor.
Ipinaalam rin sa akin na wala akong makukuhang pinansyal na suporta o pera sa
pagsali sa pag-aaral na ito. Tanging libreng serbisyo ng mga doktor at paggamit ng mga
pasilidad ng Ospital gaya ng phototherapy unit ang aming makukuha. Naipaliwanag rin sa
akin na ang mga impormasyon tungkol sa aking anak ukol sa pagsali n’ya sa pag-aaral na
ito ay hindi ibubunyag at mananatiling kumpidensyal na naaayon sa batas, liban sa
gumagawa ng pagsusuring ito. Ang mga imposmasyon mula sa pagsusuring ito ay maaring
mailathala o maibigay sa ibang taong gumagawa ng pagsusuri, ngunit ang pagkakakilanlan
sa akin at sa aking anak ay hindi ibubunyag.
Alam ko na ang pagsali sa pagsusuri ay dapat kusang-loob. Maaari kong bawiin ang
pakikilahok sa pagsusuri ng aking anak kahit anong oras at hindi magbabago ang
pagbibigay ng lunas sa aking anak sa ano mang paraan. Lahat ng aking katanungan ukol
sa pagsusuring ito ay nasagot ng may katiyakan at lubos kong nauunawaan. Binigyan rin
ako ng sapat na oras para pag-isipan ang pagbibigay ng aking pahintulot.
Kung ako man ay may katanungan, maaari kong kausapin si Dr. Viel Bagunu sa
telepono bilang: 8826316 loc 258 o cellphone: 09561342583. At kung ako man ay may
katanungan sa kung paano nabuo ang LED phototherapy ay maari kong kausapin si Engr.
Paul Cabacungan ng Ateneo Innovation Center sa telepono bilang: 9272147 o cellphone:
09183860216.
Sa aking paglagda ay ipinapahiwatig nitong nabasa at naunawaan ko ang mga
nakatala at kusang-loob na pinahihintulutan ko ang aking anak na lumahok sa naturang
pag-aaral.
_____________________________ _______________
Pangalan ng pasyente Petsa
______________________________ ________________
Pangalan at lagda ng magulang Petsa
______________________________ ________________
Pangalan at lagda ng saksi Petsa
________________________________ ________________
Pangalan at lagda ng kumukuha ng pagsang-ayon Petsa
APPENDIX B
SPECIFICATIONS OF LED UNIT
The LED phototherapy unit was custom made in collaboration with Ateneo
Innovation Center , a non-profit research organizationin Ateneo de Manila University under
the School of Science and Engineeringwith the following specifications: light source using
blue light emitting diode (LED) giving off light in the wavelength spectrum of 460 to 490-nm
(blue-green light region) with peak spectral irradiance of >30uW/cm2/nm at a recommended
treatment distance of 30 cm above the patient.
Pilot study was done prior to this randomized contolled trial to test efficacy and
safety of the phototherapy. Prior to its use for the study, testing of the equipment and safety
precaution was built into the phototherapy device.
The prototype low cost LED phototherapy device was made of 20 pieces blue LED
lamps connected in parallel, with each bulb giving 3 watts power, hence a total power rating
of 60W
A spectro -Vis Plus ( Vernier) was used to determine the spectrum of the LED lamps.
The emission spectrum was found to be 46476.446 nm , which falls within the most effective
range (460-490nm ) for phototherapy
The inensity of the LED lamp was 143 nm, measured using a light intensity meter.
The calculated value of the irradiance was 54 uW/cm2/nm. This value is almost 2x higher
than the minimum recommended irradiance (30 required for intensive phototherapy at 1m
distance.
The calculation of the irradiance:
Irradiance= measured intensity (µW/ cm2)/ range of wavelength
Irradiance= 14.3 * ( 106 µW/watt) * [( 1 m2 /10 4 cm2 )}
476.4-462.1 nm
= 59.40 µW/ cm2)/nm
The total power consumption of the prototype is 60 watts which is less that one ffth of
the commercial phototherapy light ( about 400 watts) that uses fluorescent tubes.
The unit was designed in such a way that the whole light casing can be tilted from
side to side, the metallic pipe stand height can be adjusted . the unit was placed with wheels
for mobility. The total cost for the development of the prototype equipment was
approximately Php 20, 000
APPENDIX C
SPECIFICATIONS OF CONVENTIONAL
Conventional fluorescent phototherapy will be administered with an Olidef CZ
Medphoto 6 Phototherapy Unit which has six fluorescent lamps in four 20 watts day light and
two blue fluorescents with a lamp life-time of 2,000 hours, emitting a light in the main
radiation spectrum in the range between 400nm -550nm, giving an irradiance of
15uW/cm2/nm at 30 cm distance from lamp box.
APPENDIX D
NOMOGRAM
NOMOGRAM Risk designation of term and near-‐term well newborns based on their hour-‐specific serum bilirubin values. The high-‐risk zone is subdivided by the 95th percentile track. The intermediate -‐risk zone is subdivided into upper and lower risk zones by the 75th percentile track. The low-‐risk zone has been electively and statistically defined by the 40th percentile track. (From Bhutani VK, Johnson L, Sivieri EM: Predictive ability of a predischarge hour-‐specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-‐term newborns, Pediatrics 103:6–14, 1999.) SOURCE: Nelson Textbook of Pediatrics 20th edition
APPENDIX E
Case Report Form
Patient Number: ____________________ Age of Gestation ( MI): __________________
Day of life: /sex:_____________________ Date/ Time of Birth: ____________________
Patient’s blood type: __________________ Mother’s blood type: ___________________
Weight (kg) upon admission: ___________ Feeding: _____________________________
Phototherapy: ______________________
Date/time started: ___________________ Date/time ended: ______________________
Admitting Diagnosis: ___________________________________________________________
APPENDIX F
Mother Data Collection Form
Phototherapy (Hours)
TSB (mg/dL)
Risk Zone (based on hour-specific normogram)
Complications
Rash Blister Watery stool Others
Baseline Bilirubin
24h
48h
Patient Number: _____________
DURATION (minutes )
DATE/TIME Breastfeeding Cleaning Turning Blood extraction
APPENDIX G
Patient Monitoring Form
Patient’s Number: _______________________________________________
Date/time Weight Temperature Urine output
APPENDIX H
Total Serum Bilirubin after 24 hours
Type of Phototeraphy Mean Std. Deviation N Conventional 18.1549 2.81591 49
LED 17.7452 2.31486 50
Total 17.9480 2.57010 99
Total Serum Bilirubin after 24 hours Tests of Between-Subjects Effects
Source Type III Sum of
Squares df Mean Square F Sig.
Partial Eta
Squared
Corrected Model 329.572a 2 164.786 49.784 .000 .509 Intercept 2.592 1 2.592 .783 .378 .008
Alternate Table (Independent Sample’s t-test Between Groups)
Independent Samples Test
Levene's Test for Equality of Variances t-test for Equality of Means
F Sig. t df
P-value
(α =0.05)
Mean Difference
Std. Error Difference
95% Confidence Interval of the Difference
Lower Upper
Baseline Total Bilirubin (TB)
Equal variances not assumed
5.696 .019 -2.602 87.646 .011 -1.19946 .46096 -2.11557 -.28335
BaselineTotalBilirubinTB 325.418 1 325.418 98.313 .000 .506
Type 43.449 1 43.449 13.126 .000 .120 Error 317.761 96 3.310 Total 32538.201 99 Corrected Total 647.333 98 a. R Squared = .509 (Adjusted R Squared = .499)
Total Serum Bilirubin after 24 hours Estimates
Type of Phototeraphy Mean Std. Error 95% Confidence Interval
Lower Bound Upper Bound Conventional 18.640a .264 18.115 19.165 LED 17.270a .262 16.750 17.789 a. Covariates appearing in the model are evaluated at the following values: Baseline Total Bilirubin (TB) = 20.5627.
Total Bilirubun after 48 hrs
Type of Phototeraphy Mean Std. Deviation N Conventional 15.1016 2.49606 49
LED 13.6756 2.21327 48
Total 14.3960 2.45500 97
Total Serum Bilirubin after 48 hours Tests of Between-Subjects Effects
Source Type III Sum of
Squares df Mean Square F Sig. Partial Eta Squared
Corrected Model 155.894a 2 77.947 17.334 .000 .269 Intercept 26.697 1 26.697 5.937 .017 .059 BaselineTotalBilirubinTB 106.587 1 106.587 23.703 .000 .201
a. R Squared = .269 (Adjusted R Squared = .254)
APPENDIX I
LETTER OF APPROVAL OF THE STUDY
OSPITAL NG MAKATI
Type 92.246 1 92.246 20.514 .000 .179 Error 422.701 94 4.497 Total 20681.284 97 Corrected Total 578.595 96
Total Bilirubun after 48 hrs
Estimates
Type of Phototeraphy Mean Std. Error
95% Confidence Interval
Lower Bound Upper Bound Conventional 15.400a .309 14.787 16.014
LED 13.371a .312 12.750 13.991
a. Covariates appearing in the model are evaluated at the following values: Baseline Total Bilirubin (TB) = 20.6002.
Interruption to Phototherapy
A B
Breastfeding ( every 3 hours ) 35 35
Cleaning ( minutes, 4x a day) 6.5 6.5
Blood Extraction ( minute per day) 5 5
Turning ( hours) 2.5 2.5
Sampaguita corner Gumamela Sts., Pembo, 1218 Makati City, Philippines
Tel. +632 882 6316 to 36
P h i l H e a l t h A c c r e d i t e d
S e p t e m b e r 1 , 2 0 1 5
V i e l M . B a g u n u , M . D .
D e p a r t m e n t o f P e d i a t r i c s
O s p i t a l n g M a k a t i
D e a r D r . B a g u n u ,
T h i s i s t o i n f o r m y o u t h a t y o u r r e s e a r c h e n t i t l e d “ C o m p a r a t i v e S t u d y o f L i g h t E m i t t i n g I o d i d e ( L E D ) P h o t o t h e r a p y d e v i c e v e r s u s c o n v e n t i o n a l f l u o r e s c e n t p h o t o t h e r a p y i n t r e a t m e n t o f I n d i r e c t H y p e r b i l i r u b i n e m i a a m o n g h e a l t h y t e r m i n f a n t s i n O s p i t a l n g M a k a t i h a s b e e n a p p r o v e d b y t h e R e s e a r c h a n d E t h i c s C o m m i t t e e .
B e r n a r d o D i m a c a l i , M . D .
C h a i r m a n , R e s e a r c h a n d E t h i c s C o m m i t e e