A Comparative Analysis of Intermittent and Continuous Phototherapy in Patients with Neonatal Jaundice

Aim: To compare the outcome of intermittent phototherapy versus continuous phototherapy in treatment of neonatal jaundice. Study Design: Randomized clinical trial (RCT). Place and Duration: This study was conducted at Department of pediatrics, neonatal ward, Liaquat university hospital Hyderabad/Jamshoro, from 8 January to 7 July 2020 Methodology: There were 222 neonate with jaundice, which were randomly allocated into two groups. One hundred and one neonates were in group “A” who received continuous phototherapy while 111 neonates were treated with intermittent phototherapy called group B. Phototherapy units were identical regarding their manufacture and radiance with 5 blue light tubes at a distance of 1520 cm above neonate that produced the irradiance of 20μW/cm 2 /nm at 420-470 nm. Serum bilirubin levels were measured every 12 hourly after starting phototherapy up to 48 hours. SPSS version 22 was used for data analysis. Original Research Article Mari et al.; JPRI, 33(52A): 26-31, 2021; Article no.JPRI.77607 27 Results: The average age of the neonates was 2.23±1.45 days. In this study, the reduction of bilirubin level in both groups after 12, 24, 36, 48 hours of phototherapy and at the time of discharge was not different between groups. Conclusion: Intermittent and continuous phototherapies were found to be equally effective. Because of its additional benefits, intermittent phototherapy can be adopted as a routine procedure instead of continuous phototherapy in neonatal care units, however, it needs to be confirmed by large scale RCTs.


INTRODUCTION
Yellow discoloration of skin and sclera that resulted from accumulation of un-conjugated bilirubin in underlying skin and mucosal membrane usually affects 60% of term and 80% of preterm neonates during the first week of life. It is a commonest clinical condition that require medical attention to prevent unusual consequences i.e. neurotoxicity [1,2]. In a local report in 2010, about 39.7 babies per 1000 live birth had neonatal jaundice [3]. Normally bilirubin production in neonates is 6-8 mg/kg i.e. two times higher than adults, but due to insufficiency of conjugate enzyme, the level of un-conjugated bilirubin becomes high over certain period of time, this level declines steadily. High levelsof bilirubin can cause neurotoxicity i.e. kernicterus, cognitive impairment, muscle tone disorder, deafness and sometimes death [4].
As for the prevention of neurotoxicity, there are several methods to treat hyper-bilirubinemia but phototherapy is widely used modality [5].
Usually, continuous phototherapy is routinely used but it causes separation of mother and neonate, interference of breast feeds and increased risk of adverse effects i.e. skin rash, insensible losses, retinal damage, hyperthermia and increased intestinal flow [6].
Beside the potential harms and concerns regarding phototherapy, intermittent approach can produce pleasant and ease, not only for parents and patients but even for hospital staff to accommodate more patients. Despite modification of phototherapy with decrement in light exposure without compromising the efficacy would certainly be advancement over conventional methods [7].
The present study was conducted to evaluate the efficacy of continuous versus intermittent phototherapy in treatment of neonatal hyperbilirubinemia.

Neonatal jaundice
Neonates that presented after 24 hours of age and <10 days with jaundice but classified as well baby (vitally stable, feeding well.) with their serum un-conjugated bilirubin level between 12.5mg/dl to 18mg/dl. Jaundice occurring below the age of <24 hours is considered pathological and need hospitalization. Jaundice appears >10 days of life need further workup and hospitalization.

Outcome of phototherapy
It was measured in term of serum bilirubin level after starting phototherapy at 0 hours, 12, 24, 36, 48 hours and at the time of discharge. This Randomized clinical trial was done by Nonprobability, consecutive sampling technique at Liaquat university hospital Hyderabad/Jamshoro from 8 January to 7 July 2020 (Total 6 month's duration). The sample size was calculated through openepi.com, sample size calculator with statistics of mean serum bilirubin at discharge in both study groups. Total sample size was 222 with 95% confidence of interval.
Neonate>34-week gestational age, age 24 hours to 10 days with jaundice were included in the study. Sick neonates with presumed sepsis, dysmorphic babies and neonates with comorbidities (cardiac, skeletal, renal, etc) were excluded from the study. Neonates having the history of kernicterus and exchange transfusion in siblings or having hemolytic jaundice (Hb<10 mg/dl or Retic count >10 mg/dl) were also excluded from the study.
Data was collected through questionnaire-based approach from babies admitted in neonatal ward, fulfilling the inclusion and exclusion criterias. All the information were kept confidential. The neonates were divided into two groups by lottery methods.
Group A neonates received Continuous Phototherapy ie. 2 hours on and half an hour off for whole day. Group B was received Intermittent Phototherapy ie. 12 hours on and 12 hours off (breast feeding interval of 20-30 minutes is included in off phototherapy interval. Phototherapy units were identical regarding manufacture and radiance with 5 blue light tubes at a distance of 15-20 cm above neonate that produced the irradiance of 20µW/cm 2 /nm at 420-470 nm. Serum bilirubin level was measured every 12 hourly after starting phototherapy up to 48hours. Blood sample was sent to Liaquat university hospital laboratory and analyzed by experienced Lab Technician. Serum bilirubin level was in mg/dl and was noted down on proforma. Routine newborn care, eye pad care, monitoring for sign of dehydration (decrease urinary output, dry oral mucosa, and decreaseskin turgidity) and breast feeding counseling was done in every case as per recommended protocol.
After collection of data the analysis was done by using SPSS software version 23. Mean and standard deviation was calculated for quantitative variables like age, weight and serum bilirubin at start of phototherapy and serum bilirubin up to 48 hours. Qualitative measure like gender was presented as percentage and frequencies. Student t-test was applied to compare the serum bilirubin on different points. Effect modifiers age, weight, gender was controlled through stratification. Post stratification t-test was applied and p value <0.05 was considered significant.

RESULTS
There were 222 neonates with jaundice, which were randomly divided into two groups. Most of the neonate's age were between 2 to 3 days in both the groups. The average age of the neonates was 2.56±1.77days and weight of the neonates was 2.93±0.45 kg. For Mean age, weight and Serum bilirubin at start of phototherapy with respect to both groups (

DISCUSSION
Jaundice becomes detectable to the naked eye when the total serum bilirubin level exceeds about 85μmo (5mg/100ml) and most babies become visibly jaundiced in the first week of life. Approximately 60% of full-term infants and 80% of premature infants develop hyperbilirubinemia during neonatal period. Also 5-10% of them require treatment by phototherapy [8] .  In this study the average age of the neonates was 2.56±1.77days and weight of the neonates was 2.93±0.45 kg. The difference between the mean decreases in serum bilirubin of both groups was statistically not significant. In this study, the reduction of bilirubin levels in both groups 12, 24, 36, 48 hour and at discharge after treatments were not significant. Similarly Chu L, Xue X et.al showed in their systemic review and meta-analysis study that intermittent phototherapy and continuous phototherapy were equally effective in reducing the total serum bilirubin [9].In another international study by Zhou S et.al there was no significant difference in serum bilirubin levels between continuous and intermittent phototherapy groups at 24, 48 and 72 h after treatment (P>0.050) [10].
A randomized controlled trial was done by Taheritafti R et.al in Iran that showed that, intermittent phototherapy was as effective as continuous phototherapy to treat icteric full-term neonates. The rate of serum bilirubin decline in both groups were similar after 36 hours [11] . In an Indian study by Patil MM et.al the intermittent phototherapy was as efficacious as the continuous phototherapy, the mean age at the time of admission was 76 hours and 77 hours in continuous phototherapy group and intermittent phototherapy groups respectively. Mean total serum bilirubin at 12, 24, 48 hours were 13.26 ± 2.4 mg/dl, 10.8 ± 1.72 mg/dl, 10.16 ± 0.95 mg/dl respectively for continuous and 12.6 ± 1.65 mg/dl, 10.04 ± 1.8 mg/dl, 9.1 ± 0.66 mg/dl respectively for intermittent group (p < 0.05) [12].In another similar Indian by study Suri D et.al the difference between the mean age, mean baseline bilirubin, mean follow-up bilirubin, and the mean decrease in bilirubin for both the groups was statistically not significant [13].
In an international study by Taheritafti R et.al the length of hospital stay was 2. 3± 0. 60 and 2. 46± 0. 93 days in the continuous and intermittent groups, respectively (P=0. 516) and there was no significant differences between them in respect of decrease in serum bilirubin [14].

CONCLUSION
Our study concluded that Intermittent and continuous phototherapies are found to be equally effective. Additionally it can help in reduction of hospital stay, intermittent phototherapy can be adopted as a routine procedure instead of continuous phototherapy in neonatal care units, and however, it needs to be confirmed by largescale Randomized Control Trials.

LIMITATIONS OF THIS STUDY
We did this study on healthy neonates with jaundice, so further studies can be conducted on sick neonates with jaundice. We also excluded the extreme premature neonates, so they can also be included in further studies.

CONSENT
An informed written consent was taken from parents before starting treatment.

ETHICAL APPROVAL
Ethical approval was taken from the ethical review committee of the university.