Frequency of Thrombocytopenia in Neonates Following Phototherapy in Neonatology Unit of Tertiary Care Hospital

Aim: To determine the frequency of thrombocytopenia and its severity in relation to level of indirect hyperbilirubinemia in neonates following phototherapy at tertiary care hospital. Study Design: Descriptive study Place and duration: This study was conducted at Paediatric department (neonatal ward), Liaquat University Hospital, Hyderabad, from 1 st August 2020 till 31 st Jan 2021 Methodology: All neonates who fulfilled the inclusion criteria presented at pediatric department (neonatal ward), Liaquat University Hospital Hyderabad were included in the study. After written consent, brief history was taken from the mother or family member and complete blood count (CBC) was sent to check the baseline platelet count along with total serum bilirubin, it was repeated after 48 hours of phototherapy. Results: Out of 231 neonates 70 (30.3%) developed thrombocytopenia after phototherapy. In our study 117 neonates (50.6%) were males & 114 neonates (49.4%) were females with the mean age Original Research Article Naqvi et al.; JPRI, 33(53B): 252-257, 2021; Article no.JPRI.77518 253 of 5.9307+1.6640 days. The thrombocytopenia was seen in 70 neonates (30.3%) and type of severity was mild, moderate & severe in 52(22.5%), 13(5.6%) & 5(2.2%) respectively. Conclusion: There was a decline in mean platelet count after phototherapy but it was not statistically significant. The treating doctor should also keep in mind, other causes of thrombocytopenia when the patient is receiving phototherapy.


INTRODUCTION
Although jaundice in neonates is very common but, most of the time it is physiological and don't need any treatment [1]. Neonatal jaundice is treated by phototherapy, exchange transfusion, and various drugs like Phenobarbitone and intravenous immunoglobulin [2]. Phototherapy is widely used for the treatment of unconjugated hyperbilirubinemia [3]. Although it is safe but, it is not free of side effects, like increased insensible water losses, watery diarrhea, irritability, fever, retinal damage, bronze baby syndrome, gonadal toxicity, hypocalcaemia and thrombocytopenia [4].
Although in standard textbooks there is nothing about phototherapy induced thrombocytopenia but many authors found it in their studies. Maurer HM, et al. and Pishwa N, et al. observed in their studies that phototherapy causes thrombocytopenia [5,6]. Zieve PD, et al. found effects of phototherapy on platelet [7]. During phototherapy platelets lost the ability to aggregate and release potassium, acid phosphatase, serotonin and adenosine triphosphate [8]. Electron microscope revealed depletion of cytoplasmic organelles in platelets as compared to controls [9]. Unlike other side effects, a very few international studies are currently available which depict the effect of phototherapy on platelet count with controversial & variable observations [10].
The local literature in our population is still scarce hence; the present study is relevant and specific for determining the effect of phototherapy on platelet count so that appropriate management plans can be designed to predict thrombocytopenia. The findings of study will be helpful to determine any association between the duration of exposure to phototherapy and the degree of thrombocytopenia. So, further recommendations may be made to bring changes in treatment modality as intermittent phototherapy or to decrease the duration of phototherapy with increased intensity (double phototherapy). Phototherapy: It is the most common intervention for reducing raised bilirubin levels in a newborn in which baby is placed under high intensity of white light in the visible spectrum, blue light, and special narrow spectrum (super) blue light in the range of 420-470 nanometers at a distance of 15 cm to 20 cm. This descriptive study was conducted at Paediatric department (neonatal ward), Liaquat University Hyderabad by Non probability consecutive technique from 31 st July to 2020 31 st Jan 2021. The Sample size was calculated through Rao soft by taking the prevalence of severe thrombocytopenia after phototherapy is found to be 3%, 1 with the margin of error of 2.2% and sample size was 231.

Operational Definitions
All neonates of either gender who were exposed to phototherapy for more than 48 hours for treatment of jaundice were included in the study. Neonates having features of sepsis, birth asphyxia, renal failure, IUGR, TORCH infection or congenital heart diseases (as per record of patient) were excluded from the study. The neonates already having thrombocytopenia before phototherapy, the preterm neonates with gestational age less than 34 weeks were also excluded from the study.
All neonates who fulfilled the inclusion criteria presenting in the pediatric department with yellowish discoloration of the skin and need phototherapy as per recommended guidelines were enrolled in the study. CBC with reticulocyte count and peripheral blood smear, Coomb's test, Serum bilirubin (total, direct, indirect), mother's blood group and baby's blood group were sent before starting phototherapy. Full thorough examination ofthe newbornwas performed to exclude neonatal sepsis or other co-morbidities. The phototherapy was started if needed as per recommended guidelines. After 48 hours of exposure to phototherapy, CBC report was repeated to determine any change in platelet count. At the end, researcher noted the outcome on predesigned proforma in order to determine the presence and severity of thrombocytopenia.
The data of all patients were analyzed in SPSS version 22. The frequency and percentage (%) were calculated for qualitative variables such as gender, status of gestational age, thrombocytopenia, and severity of thrombocytopenia. Mean and standard deviation was calculated for age, gestational age, duration of phototherapy, birth weight, and platelet counts before and after phototherapy. The effect modifiers like age, gender, gestational age, gestational age status, birthweight, and duration of phototherapy was addressed through stratification. The post-stratification chi-square test was applied and a p-value ≤0.05 was considered as statistically significant.

RESULTS
A total of 231 neonates exposed to phototherapy for > 48 hours were selected to conduct this study. The mean age was 5.9307+1.6640 days (

DISCUSSION
In our study thrombocytopenia was seen in 70 neonates (30.3%), and type of severity was mild in 52(22.5%), moderate in 13 (5.6%) & severe in 5 (2.2%) neonates. In a similar local study there was insignificant decrease in platelets after phototherapy. Mild thrombocytopenia was seen in 7 (2.23%) neonates, while moderate thrombocytopenia was present in 2 (0.64%) neonates [11]. In another similar Indian study 35 (35%) neonates had thrombocytopenia among them 74% had mild thrombocytopenia. In 26 (74%) neonates thrombocytopenia was present during the first day of phototherapy [12]. In a study from Nepal the mean platelet count also decreased from 258×103 cells/mm3 to 241×103 cells/mm3 with a p-value of 0.041 which was significant [13].
The phototherapy causes decreased platelet life span along with increased production of platelets but when bone marrow is compromised then thrombocytopenia occurs [14].
In our study thrombocytopenia was common in term neonates. In Premature neonates mean Platelet Count was decreased on the first day of Phototherapy when compared with no Phototherapy which was statistically significant (p = 0.018). In the similar studies Mean Platelet Count 24 Hr after Phototherapy was significantly decreased (in preterm and term neonates both) as compared to the Mean Platelet Count before starting Phototherapy (p = 0.008) [15,16].
In our study thrombocytopenia was predominant in male gender. In a study among 190 neonates, 108(56.8%) were male and 82(43.2%) were female; Mean platelet count before initiation and just after completion of phototherapy were (2, 49,321.0526± 89,460.2101)/µL and (2, 22,436.8421 ± 88,538.7173)/µL respectively. Decrease in platelet count just after completion of phototherapy was statistically significant [11]. The limitation of our study was single center study and smaller sample size. Further studies with larger sample sizes are required.

CONCLUSION
In conclusion there was a decline in mean platelet count after phototherapy but it was not statistically significant. The treating doctor should also keep other causes of thrombocytopenia when the patient is receiving phototherapy.

DISCLAIMER
The products used for this research are commonly and predominantly use products in our area of research and country. There is absolutely no conflict of interest between the authors and producers of the products because we do not intend to use these products as an avenue for any litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by personal efforts of the authors.

CONSENT AND ETHICAL APPROVAL
Permission was taken from the ethical review committee of university. Written and verbal informed consent was taken from the guardian (mother or father) after explaining them the purpose and procedure of the study in detail and ensuring the confidentiality.