Evaluation of Etiology and Treatment of Jaundice in Neonates Pursuit Phototherapy in a Tertiary Care Rreferral Hospital - A Prospective Cohort
Study.
T. Balasubramanian *, R. Monika, M. Ramsheed, M. Rafih, M. Salman and P. Balan
Al Shifa College of Pharmacy, Poonthavanam P.O., Kizhattur, Perinthalmanna, Malappuram Dt., Kerala 679325, India
ABSTRACT
Aim: Neonatal jaundice, affects one in two infants globally, is a major cause of hospital admissions during the neonatal period. The aim of this study was to recognize the causes of jaundice in neonate’s and to identify the efficacy of phototherapy.
Methods: A prospective cohort study was carried out among 495 new-borns with jaundice aged up to 7 days, both term and preterm in the department of neonatology for a period of 9 months. A data collection form was designed to collect the information. Neonatal and maternal assessments were done to assess the possible etiology of jaundice. Effectiveness of different treatments and phototherapy using different light sources was assessed.
Results: In our study as per the neonatal assessment, factors like low breast feeding (p=0.000), sepsis (p
=0.006), hypoxia (p =0.003) and Glucose 6 phosphate dehydronase (p=0.000) are found to highly significant to the incidence of jaundice. According to the maternal assessment, factors like maternal ethnicity (p=0.000), thyroid status (p =0.000), history of neonatal jaundice (p =0.000), use of oxytocin infusion (p =0.004) and bruising during delivery (p =0.000,) are highly significant. This study shows that the most effective treatment was found to be exchange transfusion. Phototherapy was given in 78 % of the neonates.
Conclusion: Our study results conclude that there is highly significant relationship between low breast feeding and occurrence of neonatal jaundice. We believe that highly linked factor ‘maternal history of neonatal jaundice’ will bring up new treatment, prevention trends and early diagnosis for neonatal jaundice.
Keywords: Neonatal jaundice, Etiologies, Treatment options, Phototherapy 1. Introduction
Neonatal Jaundice is observed during the first weeks of life in approximately 60% of term infants and 80% of preterm infants.1, 2 An imbalance between bilirubin production and conjugation is the main mechanism of jaundice, which leads to an increase in bilirubin levels. This imbalance often occurs due to the immature liver and the rapid breakdown of red blood cells, which may be involved with several factors.3, 4 Nevertheless, diagnosis of new born jaundice and its management will play an important role in the health of new born.5 Most new born babies have physiological jaundice. It is most noticeable when the baby is 2-4 days old. 6 Identification of predisposing factors in the management of the disease is important. Thus present study aims to recognize the causes of jaundice in neonate’s pursuit phototherapy, the factors that place an infant’s at risk for developing hyperbilirubinemia and to identify the efficacy of phototherapy.
2. Material and methods 2.1 Study design
A Prospective observational cohort study was carried out from 1st November 2019 to 1st May 2020 in the department of neonatology, Kims Al Shifa multispecialty hospital, Kerala for a period of 9 months with the
aim to determine the Etiology and treatment of jaundice in neonates pursuits phototherapy. The study was approved by the ethics committee of Kim’s Al Shifa hospital (KAS/ADMN/AC/EC/154/216).
2.2 Procedure
A total of 495 new-born patients in Neonatal department diagnosed with jaundice were selected based on inclusion and exclusion criteria. The nature, type or intention of the study was explained to the patients by direct patient interaction. Participants (parents) were then given time to decide whether or not to participate. If they decided to participate, written consent was obtained. A data collection form was designed to collect the information necessary for the study. The form consists of the details: Patient demographics, Neonatal assessment, Feeding pattern, Maternal assessment and Laboratory results. Sources of Data were Patients case record, Patient’s prescription and Direct interactions with physician. Demographic profiles, details of disease and medications were collected from patient’s case records. The severity of symptoms of Treatments measured using assessment of severity of symptom.ms threshold table. Careful clinical neonatal and maternal assessments were done to assess the possible etiology of jaundice. Effectiveness of the different treatment options, and phototherapy using different light sources, colours and emission spectrum was also evaluated in given population.
2.3 Statistical Analysis
The collected data for the study were compiled and analysed using SPSS version19. Chi-square test, student t test were used wherever found suitable and necessary interpretations were made. P value <0.05 was considered as significant.
3. Results
In our study as per the neonatal assessment many factors are significantly linked to the occurrence of jaundice and some factors are not. Factors like low breast feeding (26.5%, p =0.000, df=1), sepsis (7.8%, p =0.006, df=1), hypoxia (9.3%, p =0.003, df=1), G6PD (13.5%, p =0.000, df=1) and blood group incompatibilities (14.7%, p=0.000,df=1) are found to highly significant to the incidence of jaundice, and factors like gestational age (93.7%, p =0.015, df= 1), and cephalohematoma (4.4%, p=0.043, df=1) are significantly linked to the occurrence of neonatal jaundice. It is also observed that factors like UTI (1.2 %. p =0.298, df=1), gender (82.2%, p =0.298, df=1), Gilbert syndrome (6%, p =0.463, df=1), Dubin-Johnson syndrome (4%, p =0.549, df=1) are not significantly associated with neonatal jaundice (Figure 1, Table 1).
According to the maternal assessment, factors like maternal ethnicity (62.2%, p =0.000, df=2), thyroid status (8.1%, p=0.000, df=1),history of neonatal jaundice (71.1%, p =0.000, df=1), use of oxytocin infusion (8.7%, p =0.004, df=1), mode of delivery (61.4%), bruising during delivery (14.7%) and history of anemia (1.4%) are highly significant (p =0.000) to the occurrence of neonatal jaundice and factors like Maternal Hb count (2.4%, p =0.138, df=1), platelet count (2%, p =0.177, df=1), reticulocyte count (2%, p =0.672, df=1), maternal age (4%, p =0.549, df=1), gestational DM (11.1%, p =0.352, df=1), Number of delivery (3.2%, p
=0.086, df=1), delayed cord cutting (1.6%, p =228, df=1), History of abortion(2%, p =0.672, df=1) and history of thalassemia (1.8%, p =0.298, df=1) are not linked to the incidence of neonatal jaundice (Figure 2, Table 1).
Our study shows that the most effective treatment was found to be exchange transfusion, then IV immunoglobulin, phototherapy, breast feed correction, and antibiotic therapy in the same order (Figure. 3, Table 2). In phototherapy the most effective light source was found to be LED, then FT and Halo spot light [Fig. 4, Table 2]. The most effective colour ( used in phototherapy light) was found to be green than blue as per our study (Figure 5, Table 3), and we are not able to find the effective emission spectrum used in phototherapy as all of them receive the same emission spectrum (350-550nm) and nothing to be compared with (Table 2, and 3).
Item Category
Before treatment (micromol / liter in infants aged 96 hours or more )
Total
Pearson chi square test
Pvalue df
>350 >450 1. Gestational Age
34 to 37 weeks 31 (6.3%) 0 (0%)
495 5.906a 0.015 1 38-42 weeks 389
(93.7%) 75 (100%)
2.Maternal ethnicity
Black 109 (26%) 0 (0%)
495 53.667a 0 2
White 78 (18.6%) 0 (0%)
Asian 233
(55.5%) 75 (100%)
3. Gender Male 344
(81.9%) 63 (84%)
495 .191a 0.662 1 Female 76 (18.1%) 12 (16%)
4. Term
Term babies 131 (31.2%)
47 (62.7%)
495 27.378a 0 1
Pre Term babies 289 (68.8%)
28 (37.3%) 5. Breast feeding
pattern
Low breast feeding
131
(31.2%) 0 (0%)
495 31.812a 0 1
Normal breast feeding
289
(68.8%) 75 (100%) 6.
Cephalohematoma
with
cephalohematoma 22 (5.2%) 0 (0%)
495 4.111a 0.043 1 without
cephalohematoma 398
(94.8%) 75 (100%) 7. Sepsis
With Sepsis 39 (9.3%) 0 (0%)
495 7.560a 0.006 1 Without Sepsis 381
(90.7%) 75 (100%) 8. Hypoxia With Hypoxia 46 (11%) 0 (0%)
495 9.056a 0.003 1 Without Hypoxia 374 (89%) 75 (100%)
9. G6PD With G6PD 67 (16%) 0 (0%)
495 13.837a 0 1
Without G6PD 353 (84%) 75 (100%) 10. Gillbert
syndrome
With Gillbert
syndrome 3 (0.7%) 0 (0%)
495 0.539a 0.463 1 Without Gillbert
syndrome
417
(99.3%) 75 (100%)
11. Dubin johnson syndrome
With Dubin johnson
syndrome
2 (0.5%) 0 (0%)
495 0.359a 0.549 1 without Dubin
johnson syndrome
418
(99.5%) 75 (100%) 12. Blood group
incompatibility
With Blood
group 0 (0%) 73
(97.3%) 495 479.517a 0 1
incompatibility Without Blood group
incompatibility
420 (100%) 2 (2.7%)
13.Urinary tract infection
With UTI 6 (1.4%) 0 (0%)
495 1.085a 0.298 1 Without UTI 414
(98.6%) 75 (100%) 14. High Hb count
High Hb 12 (2.9%) 0 (0%)
495 2.196a 0.138 1
Normal Hb 408
(97.1%) 75 (100%) 15. Platelet count
High Platelet
count 10 (2.4%) 0 (0%)
495 1.823a 0.177 1
Normal 410
(97.6%) 75 (100%) 16. MCV
Abnormal 2 (0.5%) 0 (0%)
495 0.359a 0.549 1
Normal 418
(99.5%) 75 (100%) 17. Hct
High 10 (2.4%) 0 (0%)
495 1.823a 0.177 1
Normal 410
(97.6%) 75 (100%) 18. WBC
High 10 (2.4%) 0 (0%)
495 1.823a 0.177 1
Normal 410
(97.6%) 75 (100%) 19. Reticulocyte
count
Abnormal 1 (0.2%) 0 (0%)
495 0.179a 0.672 1
Normal 419
(99.8%) 75 (100%) 20. Maternal weight
Abnormal 2 (0.5%) 0 (0%)
495 0.359a 0.549 1
Normal 418
(99.5%) 75 (100%) 21. Maternal age
Abnormal 2 (0.5%) 0 (0%)
495 0.359a 0.549 1
Normal 418
(99.5%) 75 (100%) 22. Gestational
diabetesmellitus
With Gestational
diabetesmellitus 49 (11.7%) 6 (8%)
495 0.866a 0.351 1 Without
Gestational DM
371
(88.3%) 96 (92%) 23. Maternal thyroid
status
Abnormal 0 (0%) 40
(53.3%)
495 243.692a 0 1
Normal 420 (100%) 35
(46.7%) 24. Maternal H/o of
neonatal jaundice
had jaundice 277 (66%) 75 (100%)
495 35.910a 0 1
Do not had
jaundice 143 (34%) 0 (100%)
25. Number of Non primi mother 404 75 (100%) 495 2.953a 0.086 1
Table 1-Cross tabulation of different etiological factors and bilirubin level before treatment
delivery (96.2%)
primi mother 16 (3.8%) 0 (0%) 26. Use of oxytocin
infusion
Those use 43 (10.2%) 0 (0%)
495 8.409a 0.004 1 Those not use 377
(89.8%) 75 (100%) 27. Mode of delivery
Normal 284
(67.6%)
20 (26.7%)
495 45.037a 0 1
Caesarean 136
(32.4%)
55 (38.6%) 28. Bruising during
delivery
Suffered 73 (17.4%) 0 (0%)
495 15.291a 0 1
Not suffered 347
(82.6%) 75 (100%) 29. Delayed cord
cutting
Delayed cutting 8 (1.9%) 0 (0%)
495 1.452a 0.228 1 Normal cutting 412
(98.1%) 75 (100%) 30. PROM
Had rupture 1 (0.2%) 0 (0%)
495 0.179a 0.67 1 Had no rupture 419
(99.8%) 75 (100%) 31. History of
abortion
Had history of
abortion 1 (0.2%) 0 (0%)
495 0.179a 0.67 1 No history of
abortion
419
(99.8%) 75 (100%) 32. Drug taken by
mother during pregnancy / delivery
Taken 141
(33.6%) 0 (0%)
495 35.207a 0 1
Not taken 279
(66.4%) 75 (100%) 33. Maternal history
anaemia
Had history 0 (0%) 7 (9.3%)
495 39.762a 0 1
Had no history 420 (100%) 68 (90.7%) 34. Maternal history
of thalassemia
Had history 6 (1.4%) 0 (0%)
495 1.085a 0.29 1 Had no history 414
(98.6%) 75 (100%)
Types of
Therapy Number
Serum Bilirubin
Mean Std deviation
Mean differenc e
Std devia tion
P value
t value
Confidence interval level
Lowe r limit
Upper limit 1. Breast feed
correction 131
Before
treatment 396.7 28.59
291.49 39.02 0.00 85.48 284.7
5 298.24
after
treatment 105.2 22.23 2 Antibiotic
therapy 45
Before
treatment 365.4 11.66
287.6 14.44 0.00 133.5 283.2
5 291.94
after
treatment 77.8 8.1
Table 2 -Effectiveness of different treatment options.
Table 3- Descriptive statistics for light source used in phototherapy.
Parameter Number Mean Std.
Deviation Std.
Error
95% Confidence Interval for Mean
Min. Max.
Lower Bound
Upper Bound Serum
bilirubin (Before)
LED 180 414 54.68 4.07 405.99 422.07 350 548
FT 180 365 9.71 0.72 363.61 366.47 350 399
HALO SPOT LIGHT 18 364.3 12.46 2.93 358.07 370.47 350 389
Total 378 388.3 45.53 2.34 383.73 392.94 350 548
3 Phototherapy 378
Before
treatment 387.9 45.26
295.62 57.31 0.00 100 289.8
1 301.43
after
treatment 92.27 39.68 4 Exchange
transfusion 73
Before
treatment 474.3 16.87
379.02 50.54 0.00 64.07 367.2
3 390.82
after
treatment 95.26 58.09
5. IV.
Immunoglobulin 10
Before
treatment 488.3 31.55
335.7 115.6 0.00 9.18 253 418.39 after
treatment 152.6 140.33 6. Phototherapy
using LED 180
Before
treatment 414 54.68
327.58 57.05 0.00 77.03 319.1
9 335.98
after
treatment 86.44 38.29 7. Phototherapy
using FT 180
Before
treatment 365 9.71
270.97 40.52 0.00 89.71 265.0
2 276.93
after
treatment 94.06 40.407 8. Phototherapy
using Halo spot light
18
Before
treatment 364.3 12.46
231.83 12.77 0.00 76.96 225.4
7 238.18
after
treatment 132.4 4.04 9.Phototherapy
using blue light 310
Before
treatment 369.9 24.32
275.54 39.72 0.00 122.1 271.1 279.98 after
treatment 94.31 42.81 10.
Phototherapy using green light
68
Before
treatment 472.6 12.64
389.63 22.01 0.00 146 384.3 394.96 after
treatment 82.92 15.95
Serum bilirubin (After)
LED 180 86.44 38.29 2.85 80.81 92.07 67 436
FT 180 94.06 40.4 3.01 88.12 100 64 239
HALO SPOT LIGHT 18 132.4 4.047 0.95 130.43 134.45 125 137
Total 378 92.26 39.58 2.03 88.26 96.26 64 436
Differenc
e in
Serum Bilirubin
LED 180 327.6 57.05 4.25 319.19 335.98 94 426
FT 180 271 40.52 3.02 265.01 276.93 143 324
HALO SPOT LIGHT 18 231.8 12.77 3.01 225.47 238.18 213 259
Total 378 296.1 57.48 2.95 290.25 301.88 94 426
0 100 200 300 400 500 600
factors
Figure 1- Neonatal Assessment.
Figure 2 - Maternal Assessments.
0 50 100 150 200 250 300 350
400 mean…
Figure 3 -Effectiveness of different treatments on given population.
0 50 100 150 200 250 300 350
LED(no:180) FT(no:180) Halo spot light(18)
mean difference
Figure 4 -Effectiveness of light source used in phototherapy
0 100 200 300 400
Blue color(310) green color(68)
mean difference
Figure 5- Effectiveness of light colour used in phototherapy.
4. Discussion
In our study, 93.7 % were having gestational age between 38-42 weeks and 6.3% were between 34-37 weeks.
Study conducted by Sarici SU et al has described that risk of hyperbilirubinemia significantly increases with decreasing gestational age [7,8]. Our study results conclude that there is highly significant relationship between low breast feeding and occurrence of neonatal jaundice (p =0.000, df=1). A study conducted by Ying-Juang Chen et al reveals that increased breast feeding and shorter hospital stays were suggested as contributing factors to the significant rate of hyperbilirubinemia and the reemergence of kernicterus. 9, 10 Our study results shows that cephalohematoma (p =0.043, df=1), sepsis (p =0.006, df=1) and hypoxia (p =0.003, df=1) are highly significant with the occurrence of neonatal jaundice. In our study G6PD is found in 13.5% of neonates, which means G6PD is a leading cause of neonatal jaundice. A study conducted by Ching-shan
Huang et al describes that Glucose-6-phosphate dehydrogenase is the most common human genetic enzymopathy, which is closely associated with neonatal hyperbilirubinemia.11 In our study 6% of newborn have Gilbert syndrome (GS). A study conducted by John D. Bancroft et al proves that the newborn infants with the molecular markers for Gilbert syndrome have an accelerated increase in neonatal jaundice during the first 2 days of life.12 Our study describes that blood group incompatibility was highly significant with the occurrence of neonatal jaundice especially ABO incompatibility (p =0.000,df=1). Our research describes that maternal thyroid status was highly significant with the occurrence of neonatal jaundice (p =0.000, DF=1). In our study 71.1% had a history of neonatal jaundice. To the best of our knowledge, this is the first study focus on the factor maternal history of neonatal jaundice and found a positive relationship like this. Our study describes that use of oxytocin during delivery was highly significant with the occurrence of neonatal jaundice (p =0.004, df=1). Oxytocin also increases RBC lysis while passing through the vessels, thus leading to hyperbilirubinemia.13,14,15,16
Out of the total of 495, 304 baby born by normal delivery and rest of 191 born by cesarean. Our study concludes that baby born by normal delivery was highly significant with the occurrence of neonatal jaundice (p =0.000,df=1). A study conducted by Ehsan Garosi et al shows that the mean total bilirubin levels was significantly higher in newborns delivered vaginally compared to cases born by cesarean section [15].Out of the total 495, 14.7% neonates had suffered bruising during their delivery. This results shows that bruising during delivery is a source of development of jaundice. A study conducted by S.W.D’souza et al describes that, in the neonatal period, babies had excessive scalp bruising surrounding an area of skin damage and subcutaneous necrosis where the spiral electrode had been applied.17
We observed that there is highly significant correlation between steroid drug taken by mother before or during pregnancy and neonatal jaundice (p =0.000, df=1). Our study shows that maternal history of anaemia was highly significant with the occurrence of neonatal jaundice (p =0.000, df=1).Study conducted by Audrey K. Brown have a different opinion that infants born to women with sickle cell disease are at greater risk of neonatal jaundice.18 Breast feed correction is given for those neonates who develop jaundice as a result of abnormal feeding patter or low breast feeding, that is low breast feeding is found in 26.5% of neonates. The one of the main limitation, in finding the effectiveness of different treatment is that same individual receives multiple therapies and the exposure group is different in receiving different treatments. Phototherapy is a safe, effective method for decreasing or preventing the rise of serum unconjugated bilirubin levels and reduces the need for exchange transfusion in neonates. Phototherapy was given in 378 neonates. A study conducted by Michael W et al has proved that phototherapy was 85% effective in preventing TSB≥25mg/Dl.19
5. Conclusion
Our study results conclude that there is highly significant relationship between low breast feeding and occurrence of neonatal jaundice. So, we suggest the 10 steps put forward by WHO to successful breast feeding. To the best of our knowledge, this is the first study focus on the factor maternal history of neonatal jaundice and found a positive relationship like this. We believe that highly linked factor ‘maternal history of neonatal jaundice’ will bring up new treatment, prevention trends and early diagnosis for neonatal jaundice.
Our study concludes that the most effective treatment was found to be exchange transfusion, then IV immunoglobulin, phototherapy, breast feed correction and antibiotic therapy in the same order. In phototherapy the most effective light source was found to be LED, then FT and Halo spot light. Due to high incidence of G6PD deficiency, it is recommended to introduce qualitative test of this enzyme as a routine laboratory investigation for all icteric neonates so as to get an early diagnosis and to avoid complications.
Conflicts of interest
The authors declare no relevant conflicts of interest.
Acknowledgements
We acknowledge the valuable comments and suggestions by Dr Moideen Babu, Consultant Neonatologist, during this project. The authors would like to thank the staff, Department of Nephrology, Al Shifa Hospital, and Department of Pharmacy Practice, Al Shifa College of pharmacy for supporting this work.
Funding Source
Funding for the research project was provided by Al ShifaCollege of Pharmacy, Shifa Institute of Medical Sciences, Shifa Medicare Trust, Perinthalmanna, Kerala.
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