SUPPLEMENTAL INTRAVENOUS FLUIDS AS A TREATMENT MODALITY FOR SEVERE NON-HEMOLYTIC NEONATAL HYPERBILIRUBINEMIA By

Background: Phototherapy is a standard treatment for neonatal hyperbilirubinemia. During phototherapy, since photoproducts that cause the decrease in serum bilirubin are eliminated in bile and urine, so adequate hydration should enhance the effectiveness of phototherapy. Aim of work: To evaluate the role of intravenous (IV) fluid supplementation in decreasing total serum bilirubin (TSB) levels and duration of phototherapy in severe non-hemolytic neonatal hyperbilirubinemia. Patient and Methods: This prospective study was carried out on 48 full-term neonates with indirect non-hemolytic hyperbilirubinemia in the neonatal intensive care unit (NICU), at Menoufia University Hospitals. Included neonates were assigned randomly to receive either intravenous fluid during the first 8 hours of phototherapy in addition to breast milk (Group 1, n=24) or exclusive breast milk (Group 2, n=24). TSB was documented at presentation and then at 12, 24, 48, 72, 96, 120, and 144 hours after admission. Both groups' rates of TSB reduction and the duration of phototherapy were compared. Result: There was a significant difference in mean TSB (19.62 in group 1 versus 18.98 in group 2). Following IV fluid supplementation, TSB levels showed significant reduction at 12, 24, 48, 72-and 96-time hours (p<0.001) in group 1 (supplemented IV fluid group) compared to exclusive breast milk (Group 2). Moreover, supplemented IV fluid group had a significantly shorter duration of phototherapy and NICU stay. Conclusion: Additional IV fluid supplementation during the initial 8 hours with phototherapy in neonatal hyperbilirubinemia may considerably shorten the overall phototherapy time and TSB level in severe non-hemolytic newborn hyperbilirubinemia.


INTRODUCTION
Jaundice is an extremely prevalent clinical condition in the neonatal intensive care unit (NICU).Approximately 60% of healthy newborns develop clinical jaundice within the first week of life.
Significantly, elevated bilirubin levels may cause bilirubin encephalopathy, followed by kernicterus, which can cause severe permanent neurodevelopmental disabilities (Coelho & Apetato, 2016).Bilirubin typically peaks between 3 and 5 days of age, but it may continue to rise through factors that limit bilirubin clearance, such as poor feeding, infection, or prematurity (Elhaj YM and Hamad, 2020).
The prevalence of hyperbilirubinemia has been found to vary seasonally, rising during the summer.The incidence and severity of jaundice in neonates can rise because of subclinical dehydration caused by evaporative losses and inadequate breastfeeding.At presentation, three-fourths of newborns with severe hyperbilirubinemia have subclinical dehydration (Hansen et al., 2020).In severe neonatal jaundice, phototherapy and exchange transfusions may be required to gradually lower the serum bilirubin levels.Phototherapy can cause adverse reactions including diarrhea, skin rashes, dehydration, hyperthermia, interrupted feedings, and a reduction in mother-baby bonding.The resulting photoproducts from phototherapy are eliminated in both urine and bile decreasing serum bilirubin levels (Jain et al., 2017).
Fluid supplementation may be beneficial in the treatment of severe hyperbilirubinemia.A higher rate of bilirubin reabsorption from the intestine may follow a reduction in enterohepatic circulation brought on by fluid supplementation.Further, it seems that additional fluid treatment may reduce serum bilirubin, increase renal blood flow and urine production, and eventually enhance the elimination of water-soluble photo isomers in urine (Kaur et al., 2018).Jaundiced neonates may get sleepy from high serum bilirubin levels.This study aimed to evaluate the role of IV fluid supplementation in decreasing TSB levels in severe nonhemolytic neonatal hyperbilirubinemia and to observe its effect on the duration of phototherapy.

Ethical consideration:
1. Approval by the local ethical committee was obtained before the study.
2. Written informed consent was obtained from patients or their legal guardians.
3. The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of the article.
4. All the data of the patients and results of the study are confidential and the patients have the right to keep them.
5. The authors received no financial support for the research, authorship and /or publication of the article.

Sample size:
(Kaur et al., 2018) do a similar study, at a power of 80% and a confidence level of 95%.The sample size was calculated and found to be 30 subjects.And this will be increased to 34 subjects to avoid the dropout of the patients.17subject in each group with a ratio of (1:1).

Inclusion criteria:
All neonates admitted to the NICU with indirect exaggerated physiological hyperbilirubinemia were included provided they full fill the following criteria: • Full term healthy birth.
• Gestational period more than 37 wks.
• On breastfeeding and or formula feeding.
• Total serum bilirubin level of more than 18 mg/dl.
• Initial serum C-reactive protein is negative.
• Neonates with major congenital anomalies.
• Neonates with inborn errors of metabolism.

Study design:
All neonates were subjected to the following: 1. Complete history taking with stress on (antenatal, natal, and post-natal history), 2. General examination including vital signs, body weight, hydration status, and local systemic examination (heart, chest, and abdomen).

Rh and blood grouping for
mother and babies.

Coombs test (DIRECT).
Methods: In our study, we collect 48 patients randomly divided into two groups: Group 1: 24 neonates on breastfeeding on demand or formula feeding (20 ml of milk every 3 during admission) with extra IV fluid supplementation of normal saline /D5 (3:1) over period of 8 hrs in the first day of admission through peripheral vein.
Group 2: 24 neonates receiving breast milk or formula only in the same schedule as group 1, Both groups received the same type of LED continuous triple phototherapy.The eyes were protected from the light by eye shield to avoid retinal damage.To expose the most skin to light, the posture was regularly changed.Neonates were only ever brought out to be fed or change wet diapers and were always kept under phototherapy.Follow-up of TSB was done at time points 12,24,48,72,96,120, and 144 hours of admission with a comparison between both groups regarding TSB level and duration of phototherapy.

Statistical Analysis:
The analysis was carried out using SPSS version 22 and R version 4.1 (IBM, United States).Continuous variables were presented in terms of mean and standard deviation.Fisher's Exact tests and chi-square tests were used to compare the proportion of patients in each therapy group.A p-value <0.05 was considered significant.

RESULTS
All results will be demonstrated in the following tables and figures: This table shows insignificant differences regarding demographic characteristics between both groups.

Figure (1): Serum bilirubin level at different time points
This figure shows significant differences regarding serum bilirubin level between both groups.

Few
studies have shown that increasing IV fluid administration may decrease TSB levels more rapidly and lessen the need for exchange transfusions.Increased renal excretion of bilirubin, diluted serum bilirubin, and decreased enterohepatic circulation may all result from the more fluid supply (Kaur et al., 2018; Lai et al., 2017).However, several studies have shown no association between the provision of more IV fluid and a reduction in TSB (Morshed et al., 2017).