Exploring The Role of Peroxisome Proliferator- Activated Receptor Agonists (Fenofibrate) in Neonatal Jaundice Prevention

Exploring The Role of Peroxisome Proliferator- Activated Receptor Agonists (Fenofibrate) in Neonatal Jaundice Prevention | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Exploring The Role of Peroxisome Proliferator- Activated Receptor Agonists (Fenofibrate) in Neonatal Jaundice Prevention Rania Mohamed Abdou, Nancy Mohamed Abo Shady, Hala Sedky Gomaa Rohaim, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5938163/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Jan, 2026 Read the published version in Egyptian Liver Journal → Version 1 posted You are reading this latest preprint version Abstract Background: Neonatal jaundice is one of the most prevalent illnesses in neonates, requiring care and treatment. Fenofibrate is a lipid-lowering drug that enhances the conjugation and excretion of bilirubin. Previous studies have suggested the usefulness of fenofibrate for the treatment of indirect hyperbilirubinemia in neonates. Objective: To evaluate the role of fenofibrate in neonates with neonatal jaundice near the level of phototherapy. Patients and Methods: seventy- five full-term infants with neonatal jaundice near the level of phototherapy were randomly divided into three groups: single-dose group: 25 neonates received a single oral dose of 10 mg/kg of non-micronized fenofibrate and an oral dose of an equivalent amount of distilled water as a placebo . Double-dose group: 25 neonates received two oral doses of 10 mg/kg non-micronized fenofibrate. The control group included 25 neonates who received two oral doses of an equivalent amount of distilled water as a placebo. Results: The double-dose group had the highest significant drop in transcutaneous bilirubin (TCB) starting from 12 to 48 h after drug intake and the highest drop in total serum bilirubin (TSB) starting from 12 h to the 5 th day in comparison to the single-dose group and the controls. The single-dose and double-dose groups had a significantly lower incidence of the need for admission and phototherapy than the control group (P=0.009). The double-dose group had a significantly higher incidence of drug side effects than the single-dose group (P< 0.001), mainly in the form of abdominal distension (P=0.008); however, only minor treatment was required. Conclusion: Fenofibrate can significantly decrease bilirubin levels in full-term neonates with neonatal jaundice near the level of phototherapy, with no need for admission and phototherapy management. The drug was well-tolerated and safe. Double-dose treatment with fenofibrate significantly lowered TSB with no significant increase in side effects when compared to the single-dose group. full term neonate neonate neonatal jaundice indirect hyperbilirubinemia fenofibrate peroxisome proliferator Figures Figure 1 Figure 2 Figure 3 Introduction Hyperbilirubinemia is a common cause of diagnostic workup and therapeutic intervention in neonates. The prevalence of indirect hyperbilirubinemia (IHB) in term and preterm infants ranges from 60–90%. The excessive production of bilirubin (as a catabolic product of heme-containing molecules) or reduction in its elimination leads to increased serum bilirubin levels ( 1 ) . Fibrates are a class of phenoxy-isobutyric acid derivatives that are peroxisome proliferator-activated alpha receptor agonists. Fibrate, a lipid-lowering drug, can enhance bilirubin conjugation and excretion through induction of uridine diphosphate glucuronosyltransferase ( 2 ) . Additionally, clofibrate transfers albumin-bound bilirubin to hepatocytes and induces hepatic uptake and conjugation of bilirubin ( 3 ) . A single dose of fenofibrate (10 mg/kg) as an adjuvant to phototherapy in neonates with hyperbilirubinemia is associated with a significant reduction in serum bilirubin levels ( 3 ) . Fenofibrate appears to be an effective and safe drug for the treatment of neonatal IHB, consistent with the results of a previous study ( 4 ) . Many neonates are currently diagnosed with neonatal jaundice, either physiological or pathological, with levels reaching the phototherapy threshold and needing neonatal intensive care unit admission due to dehydration from the weather, scanty breast milk, or other benign causes that usually do not elevate the bilirubin level to photo therapy threshold. The use of a preventive drug that helps to decrease bilirubin levels before reaching the phototherapy threshold would be very useful. Therefore, this study aimed to evaluate the preventive role of fenofibrate in term neonates with neonatal jaundice. Subjects and Methods Patients: The present double-blind controlled clinical trial was performed on 75 full-term neonates with indirect hyperbilirubinemia in the first 10 days after birth. Neonates were observed in the neonatology clinic at Pediatrics Hospital, Ain Shams University Hospital, Cairo, Egypt. The inclusion criteria were as follows: full-term neonates(37 to 41 weeks gestational age), appropriate for gestational age, weight between 2500 to3500 gm infants, and indirect hyperbilirubinemia, which was evident on clinical examination and confirmed by transcutaneous and serum bilirubin measurement near but below the level of phototherapy according to the age-specific charts (5) ; (neonates were included if the transcutaneous bilirubin was above 12 mg/dl and less than18mg/dl; and were confirmed by total serum bilirubin level measurement before enrollment, measures above this will be indicative for initiation of phototherapy). Inadequate breastfeeding, exaggerated neonatal jaundice, and dehydration were the main causes of indirect hyperbilirubinemia. Hemolytic causes of neonatal hyperbilirubinemia were excluded from the study, this was confirmed by complete blood count, reticulocytic count, direct and indirect combs test and blood group typing for the mother and the neonate (ABO and RH). Newborns with congenital malformations, conjugated hyperbilirubinemia, bilirubin levels reaching exchange transfusion and phototherapy thresholds, ABO or Rh incompatibility, G6PD deficiency, skin abrasions, and infections were excluded. The included neonates were divided randomly (closed envelope simple randomization) into three groups: single dose group : 25 full-term neonates who received a single oral dose of 10 mg/kg of non-micronized fenofibrate (lipanthyl 300 mg ®)diluted in distilled water and an oral dose of equivalent amount of distilled water as a placebo, 24 h a part ( 3 ) . Double-dose group : 25 full-term neonates who received two oral doses of 10 mg/kg of non-micronized fenofibrate diluted in distilled water for 24 h ( 3 ) . Control group : 25 full-term neonates gestational age and weight matched to the other groups and who received two oral doses of equivalent amount of distilled water as a placebo 24 h apart. The three groups were examined for adequate breast and artificial feeding and were counselled to perform correctly. The type of feeding (breastfed versus bottle-fed) was matched between the groups to eliminate any potential confounding effect. Methodology: All patients underwent antenatal and natal histories and clinical examinations. Laboratory investigations included Initial Transcutaneous bilirubin levels (TCB) after birth during regular follow-ups. Transcutaneous and serum bilirubin levels were measured before starting the drug or placebo, and then at 12, 24, 36, 48 h, and 5 days after drug intake. Transcutaneous measurements were recorded using a Drager Jaundice Meter JM 105 from the forehead, sternum, and knees. The mean of the three readings was calculated. Laboratory tests done included : Total serum bilirubin level (TSB) was obtained via venipuncture under aseptic conditions. Serum bile acid was measured initially and 48 h after administration of the drug. Complete blood count, reticulocytic count, direct and indirect combs test and blood group typing for the mother and the neonate (ABO and RH) were done to exclude hemolytic causes of neonatal jaundice. All the patients were followed up for feeding and weight. Participants were sent home and scheduled to visit regularly, as needed in the study. Clinical trials registration: This Study was registered on the clinical trials.gov registry number: NCT06451900 https://clinicaltrials.gov/study/NCT06451900 Sample size calculation: A sample size of 75 neonates was calculated by using power analysis and sample size software 15 (Version 15.0.10) for sample size calculation, setting power at 80%,at significance level 0.05,using a two-sided two- sample unequal-variance t-test and after reviewing previous study results ( 2 ) showing that the mean serum bilirubin level after 48 hours in neonates with neonatal jaundice who took one dose of fenofibrate was significantly lower than those didn’t took fenofibrate(10.05 ± 1.58 versus 12.08 ± 2.44 respectively ); based on that and after considering 20% drop out rate. Data management and analysis Data were coded, tabulated, and analyzed using the Statistical Package for the Social Sciences version 28 (IBM Corp., Armonk, NY, USA). Data were summarized using mean, standard deviation, median, minimum, and maximum in quantitative data, and frequency (count) and relative frequency (percentage) for qualitative data. To compare categorical data, the chi-square (χ2) test was performed. Exact test was used instead when the expected frequency is less than 5 ( 6 ) P-values less than 0.05 were considered as statistically significant Results One hundred and fifty neonates were evaluated for potential inclusion in the study. Twenty-five were excluded based on the inclusion criteria, while thirty were excluded due to inadequate feeding and weight gain. Nine subjects were lost to follow-up, and eleven did not provide consent (Fig. 1 ) The demographic and anthropometric measurements of neonates were comparable. Blood group distribution was equivalent among mothers and their neonates, with no statistically significant differences observed between them. Patients in all groups were monitored to assess their feeding patterns, and all were found to maintain consistent feeding modes, with regular bowel movements and adequate, comparable weight gain, thus negating its potential effect on the decrease in bilirubin levels (Table 1 ). Table 1 Comparison between studied groups regarding anthropometric, demographic data, type of feeding, mode of delivery and blood group. single dose group Double dose group Control group P value Gestational age (weeks) 37.92 ± 0.81 37.92 ± 0.76 37.6 ± 0.65 0.220 Weight (kg) 3.02 ± 0.27 3.06 ± 0.25 3.21 ± 0.24 * 0.024* Age (days)** 6 (4–8) 6 (4–9) 7 (5–10) 0.056 Sex Female 11 (44.0%) 8 (32.0%) 12 (48.0%) 0.489 Male 14 (56.0%) 17 (68.0%) 13 (52.0%) Delivery NVD 5 (20.0%) 4 (16.0%) 5 (20.0%) 1 CS 20 (80.0%) 21 (84.0%) 20 (80.0%) Feeding Artificial 1 (4.0%) 0 (0.0%) 0 (0.0%) 0.720 Breast Milk 18 (72.0%) 21 (84.0%) 20 (80.0%) Mixed 6 (24.0%) 4 (16.0%) 5 (20.0%) Maternal blood group A 14 (56.0%) 15 (60.0%) 12 (48.0%) 0.896 B 2 (8.0%) 3 (12.0%) 3 (12.0%) O 9 (36.0%) 7 (28.0%) 10 (40.0%) Maternal Rh Rh -ve 0 (0.0%) 1 (4.0%) 3 (12.0%) 0.315 Rh + ve 25 (100.0%) 24 (96.0%) 22 (88.0%) Fetal blood group A 11 (44.0%) 15 (60.0%) 12 (48.0%) 0.872 B 3 (12.0%) 2 (8.0%) 3 (12.0%) AB 1 (4.0%) 0 (0.0%) 0 (0.0%) O 10 (40.0%) 8 (32.0%) 10 (40.0%) Fetal Rh Rh -ve 0 (0.0%) 1 (4.0%) 3 (12.0%) 0.315 Rh + ve 25 (100.0%) 24 (96.0%) 22 (88.0%) P-values less than 0.05 were considered as statistically significant, *: statistically significant compared to corresponding value in single dose group (P < 0.05), **: median and range#: statistically significant compared to corresponding value in double dose group (P < 0.05), NS: non-significant, S: significant, NVD: normal vaginal delivery, CS: caesarian section. The study found that neonates with a double dose of a drug had significantly lower TCB levels at 48 hours compared to those with a single dose, but the difference was not statistically significant (Tables 2 and 3 ) (Fig. 2 ). The study found a decrease in total systolic blood pressure (TSB) between the studied groups, with the decrease occurring earlier than TCB. Patients in the double-dose group had significantly lower TSB than the control group at 24 hours, 48 hours, and 5 days, and also had lower TSB than the single-dose group at 24 hours, 48 hours, and 5 days ( Table 2 & 4 ), ( Fig. 3 ) Patients in the double-dose group experienced a higher degree of drop in TCB and TSB, with TCB drop occurring at 24, 36, and 48 hours, and TSB drop at 24, 48, and 5 days. ( Table 6 & 7 ) Bile acid levels were significantly lower in the double-dose group before drug intake compared to the single-dose and control groups. ( Table 2 & 5 ) Table 2 Comparison between studied groups regarding TCB, TSB and bile acid levels. Group A (single dose) Group B (two doses) Group C (Control) P value Initial TCB 15.31 ± 1.41 15.79 ± 1.48 15.4 ± 1.26 0.442 12h TCB 14.67 ± 1.19 14.81 ± 1.38 14.71 ± 1.22 0.922 24h TCB 14.01 ± 1.25 13.73 ± 1.25 14.56 ± 1.67 0.113 36h TCB 13.28 ± 1.31 12.65 ± 1.28 13.5 ± 1.39 0.077 48h TCB 12.21 ± 1.4 10.88 ± 1.11 * 12.76 ± 1.92 # < 0.001* Initial TSB 14.54 ± 0.85 14.77 ± 0.67 14.63 ± 0.84 0.581 24h TSB 13.24 ± 0.75 12.9 ± 0.79 14.17 ± 1.87 *# 0.002* 48h TSB 12.13 ± 0.92 11.06 ± 0.73 * 13 ± 1.72 *# < 0.001* 5th day TSB 8.31 ± 1.74 6.46 ± 1.54 * 9.62 ± 1.5 *# < 0.001* Initial bile acid 14.58 ± 1.62 13.36 ± 1.67 * 14.89 ± 1.53 # 0.003* 48h bile acid 5.5 ± 2.22 4.6 ± 1.21 6.53 ± 2.03 # 0.004* P-values less than 0.05 were considered as statistically significant, TCB: Transcutaneous bilirubin TSB: Total Serum Bilirubin, *: statistically significant compared to corresponding value in Group A (P < 0.05), #: statistically significant compared to corresponding value in Group B (P < 0.05), NS: non-significant, S: significant .h: hours Table 3 Post hoc pair wise comparison 48-hour TCB between studied groups Group B (two doses) Group C (Control) 48h TCB Group A (single dose) 0.007* 0.643 Group B (two doses) < 0.001* TCB P-values less than 0.05 were considered as statistically significant, TCB: Transcutaneous. Table 4 Post hoc pair wise comparison of TSB between studied groups Group B (two doses) Group C (Control) TSB 24h Group A (single dose) 0.984 0.032* Group B (two doses) 0.002* 48h Group A (single dose) 0.006* 0.039* Group B (two doses) < 0.001* 5 day Group A (single dose) < 0.001* 0.024* Group B (two doses) < 0.001* TSB P-values less than 0.05 were considered as statistically significant Table 5 Post hoc pair wise comparison of serum bile acid between studied groups Group B (two doses) Group C (Control) Bile acid Initial bile acid Group A (single dose) 0.026* 1.000 Group B (two doses) 0.004* 48h bile acid Group A (single dose) 0.270 0.211 Group B (two doses) 0.003* P-values less than 0.05 were considered as statistically significant Table 6 Degree of drop of TCB and TSB in studied groups Group A (single dose) Group B (two doses) Group C (Control) P value TCB % drop 12h 4.02 ± 3.57 6.14 ± 2.66 4.47 ± 2.54 0.018 24h 8.41 ± 3.90 12.93 ± 4.27 5.49 ± 7.80 < 0.001 36h 13.21 ± 4.39 19.79 ± 4.86 11.03 ± 9.13 < 0.001 48h 20.19 ± 5.85 30.95 ± 4.61 15.86 ± 13.60 < 0.001 TSB % drop 24h 8.83 ± 3.19 12.69 ± 3.33 3.25 ± 9.94 < 0.001 48h 16.46 ± 6.04 25.12 ± 3.94 21.18 ± 31.70 < 0.001 5 day 42.63 ± 12.88 56.18 ± 10.60 47.25 ± 28.06 0.001 P-values less than 0.05 were considered as statistically significant, TCB: Transcutaneous bilirubin, TSB: Total Serum Bilirubin Table 7 Post hoc pair wise comparison of degree of drop of TCB and TSB between studied Groups Group B (two doses) Group C (Control) TCB % drop 12h Group A 0.022 1.000 Group B ---- 0.100 24h Group A < 0.001 1.000 Group B ---- < 0.001 36h Group A < 0.001 1.000 Group B ---- < 0.001 48h Group A < 0.001 1.000 Group B ---- < 0.001 TSB % drop 24h Group A 0.004 0.117 Group B ---- < 0.001 48h Group A < 0.001 1.000 Group B ---- < 0.001 5day Group A 0.007 1.000 Group B ---- 0.002 P-values less than 0.05 were considered as statistically significant, TCB: Transcutaneous bilirubin, TSB: Total Serum Bilirubin Patients in single and double dose groups B had lower incidences of admission and phototherapy compared to the control group. However, double dose patients had higher drug side effects, including abdominal distension, vomiting, and diarrhea. These issues were managed successfully with minor treatments (Table 8 ) Table 8 Comparison between studied groups regarding need for admission, need for phototherapy, incidence of drug side effects, symptoms and signs Group A (single dose) Group B (two doses) Group C (Control) P value Count % Count % Count % Need admission 0 0.0% 0 0.0% 5 20.0% 0.009* Reach level of phototherapy 0 0.0% 0 0.0% 5 20.0% 0.009* Drug side effects 3 12.0% 10 40.0% 0 0.0% < 0.001* Symptoms Diarrhea 0 0.0% 3 12.0% 0 0.0% 0.050 Vomiting 1 4.0% 2 8.0% 0 0.0% No 24 96.0% 20 80.0% 25 100.0% Signs Abdominal distension 2 8.0% 7 28.0% 0 0.0% 0.008* P-values less than 0.05 were considered as statistically significant, S: significant Discussion Peroxisome Proliferator-Activated Receptor (PPAR) agonists, such as fenofibrate, have been shown in this study to effectively reduce total serum bilirubin levels with minimal side effects. This suggests a potential protective role in neonates with elevated bilirubin levels near or below phototherapy thresholds. By preventing the rise of serum bilirubin levels, this approach may eliminate the need for NICU admissions for phototherapy and the associated risks. A drug administered to prevent neonates with elevated serum bilirubin levels from reaching the threshold for phototherapy has not been widely studied. To the best of our knowledge, this study is the first to evaluate the efficacy of fenofibrate as a single prophylactic drug in preventing high serum bilirubin levels in full-term infants not reaching phototherapy levels. Fenofibrate affects bilirubin metabolism by inducing conjugation and excretion of bilirubin ( 4 ) . A random sample of 75 full-term babies with hyperbilirubinemia near phototherapy levels was divided into three groups: single-dose, two-dose, and control. The neonates in our study demonstrated an early therapeutic response to the administered drug. Those who received a single oral dose exhibited significantly lower total serum bilirubin (TSB) levels compared to the control group at multiple time points: at 24 hours (P = 0.032), at 48 hours (P = 0.039), and on the fifth day (P = 0.024). Similarly, previous studies employing a single oral dose of 10 mg/kg of fenofibrate have documented a reduction in TSB levels, primarily in conjunction with phototherapy for the management of neonatal jaundice ( 1 , 3 , 7 , 8 , 9 ) . Consistent with our findings, Al-Banna et al. (2020) ( 10 ) observed a significant decrease in indirect bilirubin levels in the fenofibrate group at 24, 48, and 72 hours after initiating treatment compared to the control group (P = 0.001). Additionally, Ahmadpour-Kacho et al. (2018) ( 11 ) evaluated the effect of oral fenofibrate on TSB levels in term neonates with initial bilirubin levels exceeding 15 mg/dL. Their results showed a significant reduction in TSB levels in the intervention group compared to controls at 48 hours and on the third day of hospitalization. In contrast, the study by Prabha and Saravanan (2020) ( 12 ) reported a decline in TSB levels after 48 hours of phototherapy combined with fenofibrate; however, the difference between the fenofibrate and control groups was not statistically significant. However, it is important to note that in all the aforementioned studies, fenofibrate was used in conjunction with phototherapy, making it difficult to isolate the independent effect of fenofibrate on bilirubin levels. In contrast, our study successfully delineates the specific impact of fenofibrate in neonates with hyperbilirubinemia, as the intervention was administered without the confounding influence of phototherapy. Neonates in the double-dose group in our study demonstrated a significant and prolonged effect of the drug, evidenced by reduced total serum bilirubin (TSB) levels at both 48 hours and five days following administration. In contrast, Awad et al. (2021) ( 9 ) reported no statistically significant difference in the decline of TSB between neonates receiving a single dose of fenofibrate and those receiving a double dose at 12, 24-, 36-, 48-, or 72-hours post-intervention. Upon reviewing the literature, our study and that of Awad et al. (2021) ( 9 ) appear to be the only investigations evaluating the use of a double dose of fenofibrate in managing neonatal unconjugated hyperbilirubinemia. However, Awad et al. (2021) ( 9 ) emphasized that their findings comparing single- and double-dose regimens should be interpreted cautiously, as their study was not sufficiently powered to detect differences in efficacy. According to our findings, neonates in both the single- and double-dose groups required significantly fewer hospital admissions and phototherapy sessions compared to the control group (P = 0.009), reinforcing the potential of fenofibrate to effectively reduce bilirubin levels. Supporting our findings, Abdellatif et al. (2023) ( 13 ) conducted a meta-analysis that demonstrated fenofibrate combined with phototherapy significantly reduced the duration of phototherapy and hospital stay. They concluded that fenofibrate may serve as a safe adjunct to neonatal phototherapy. Additionally, Awad et al. (2021) ( 9 ) found that fenofibrate administration, irrespective of the dosage, was associated with a shorter duration of phototherapy and hospital stay compared to phototherapy alone. They concluded that fenofibrate is well-tolerated and associated with significant reductions in serum bilirubin, phototherapy duration, and hospital stay, with no significant adverse effects. Similarly, other studies have documented a reduction in phototherapy duration and hospital stay associated with fenofibrate use ( 1 , 7 , 10 , 11 ) Nonetheless, further large-scale randomized controlled trials are warranted to confirm these findings. In contrast, Saadat et al. (2023) ( 8 ) reported no statistically significant reduction in hospital length of stay between the fenofibrate and control groups (P = 0.612). Likewise, Prabha and Saravanan (2020) ( 12 ) observed a decrease in phototherapy duration in the intervention group, but the difference was not statistically significant. Regarding safety, neonates in the double-dose group in our study experienced a higher incidence of drug-related side effects, including abdominal distension, compared to the single-dose and control groups. However, the reported adverse effects, such as diarrhea (two episodes per day) and vomiting (once per day), were mild, did not lead to dehydration, and did not affect the infants’ weight or general condition. Based on these observations, we conclude that fenofibrate is well-tolerated, with side effects that are manageable and clinically insignificant. Consistent with our findings, Awad et al. (2021) ( 9 ) reported no statistically significant differences in adverse effects across all studied groups. Additionally, Chaudhary et al. (2016) ( 2 ) observed no side effects following a single-dose administration of fenofibrate. The majority of prior studies have focused on the use of fenofibrate in neonates with confirmed hyperbilirubinemia requiring intervention. However, the results of our study suggest that fenofibrate may also have a prophylactic role in managing hyperbilirubinemia. Neonates at risk of developing hyperbilirubinemia due to factors such as scanty breastfeeding, dehydration, breast milk jaundice, or breastfeeding jaundice could benefit from fenofibrate, potentially reducing the need for hospital admission. Limitations of the study Despite the optimized benefits demonstrated in this study regarding the effectiveness of fenofibrate in reducing serum bilirubin levels in neonates, it is important to acknowledge that this remains an experimental trial. Further large-scale studies are recommended to validate these findings and ensure their clinical applicability. Conclusion Fenofibrate, when used as a prophylactic therapy in full-term neonates with elevated bilirubin levels approaching the threshold for phototherapy, was found to be well-tolerated and effective. Its use was associated with a significant reduction in serum bilirubin levels, as well as a decreased need for phototherapy and hospital admission. Moreover, double-dose fenofibrate demonstrated a greater reduction in total serum bilirubin compared to the single-dose regimen, without a significant increase in adverse effects. Abbreviations TCB: Transcutaneous bilirubin TSB Total serum bilirubin IHB: Indirect hyperbilirubinemia Rh: Rhesus factor G6PD: glucose 6 phosphate dehydrogenase Declarations Ethical approval and consent Approval of the Research Ethics Committee of faculty of medicine Ain Shams University was obtained before the start of the research (MS 383/2023). An informed written consent was obtained from the parents or guardians of the patients or controls before inclusion in the study. Data collected was strictly confidential and only used for research purposes. The participants had the right to drop from the trial at any time they requested. Personal data of the participants were not used in the study. Consent for publication Not applicable. Personal data of the participants were not used in the study. Availability of data and materials The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding No funding was obtained for this study. Authors Contributions NA and RA provided the idea and design of the study. NA, RA, HR and MI wrote and revised the study protocol. HR was involved in the recruitment of patients, intervention, data collection, and follow-up. NA, HR, RA and MI performed the data analysis and interpretation, wrote the manuscript and revised it. All the authors reviewed and approved the final manuscript. Acknowledgement We would like to the thank all the participants in the trial. Author information Rania Mohamed Abdo: Assistant Professor of Pediatrics and Neonatology, Faculty of Medicine, Ain Shams University, Cairo, Egypt [email protected] Orcid no: 0000-0003-4799-1377 Hala Sedky Gomaa Rohaim : Pediatric resident in ministry of health and population, Egypt, [email protected] Nancy Mohamed Abo Shady: Professor of pediatrics and neonatology, Faculty of Medicine, Ain Shams University. [email protected] Mariam John Amin Ibrahim: Assistant Professor of Pediatrics and Neonatology, Faculty of Medicine, Ain Shams University, Cairo, Egypt [email protected] , ORCID number: 0000-0002-4936-8303 Tel: +201224357701 Corresponding author References Hansen TWR, Maisels MJ, Ebbesen F, Vreman HJ, Stevenson DK, Wong RJ, et al. (2020) Sixty years of phototherapy for neonatal jaundice – from serendipitous observation to standardized treatment and rescue for millions. J Perinatol.;40(2):180-93. Chaudhary, G. S., Chaudhary, V., Chaurasiya, O. S., Chandrakant, V., & Kumar, V. (2016). 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Indirect Neonatal Hyperbilirubinemia and the Role of Fenofibrate as an Adjuvant to Phototherapy. Children, 10(7), 1192. Saadat, S. H., Goodarzi, R., & Gharaei, B. (2023). Oral fenofibrate for hyperbilirubinemia in term neonates: A single-blind randomized controlled trial. Journal of Clinical and Translational Science, 7(1), e85. Awad, M. H., Amer, S., Hafez, M., Nour, I., & Shabaan, A. (2021). Fenofibrate as an adjuvant to phototherapy in pathological unconjugated hyperbilirubinemia in neonates: a randomized control trial. Journal of Perinatology, 41(4), 865-872. Al-Banna, S. M., Riad, A. N., & Anis, S. S. (2020). The effect of fenofibrate and antioxidant vitamins [D, E and C] in treatment of uncomplicated neonatal hyperbilirubinemia. Annals of Neonatology Journal, 2(1), 37-48. Ahmadpour-kacho, M., Zahed Pasha, Y., Moghadamnia, A. A., Khafri, S., & Vafaeinezhad, M. (2018). The effect of oral fenofibrate on serum bilirubin level in term neonates with hyperbilirubinemia: a randomized clinical trail. International Journal of Pediatrics, 6(10), 8317-8327. Prabha, M. S., & Saravanan, S. (2020). The efficacy of fenofibrate as an adjunct to phototherapy for neonatal hyperbilirubinemia. International Journal of Pediatrics and Geriatrics, 3(2), 73-75. Abdellatif, M., Abozaid, A. A. F., Shah, P. S., Dhouibi, N., Nguyen-Khac, T., Khleif, R., ... & Huy, N. T. (2023). Efficacy and safety of fenofibrate in combination with phototherapy for the treatment of neonatal hyperbilirubinemia: a systematic review and meta-analyses. Canadian Journal of Physiology and Pharmacology. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5938163","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":432412718,"identity":"046bad88-23f7-438e-90fa-63a477c240c5","order_by":0,"name":"Rania Mohamed Abdou","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Rania","middleName":"Mohamed","lastName":"Abdou","suffix":""},{"id":432412719,"identity":"963abd26-2c82-410a-b1a5-ae83033298ed","order_by":1,"name":"Nancy Mohamed Abo Shady","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Nancy","middleName":"Mohamed Abo","lastName":"Shady","suffix":""},{"id":432412720,"identity":"c4664eee-a17e-4975-9c0d-c3ad8403322b","order_by":2,"name":"Hala Sedky Gomaa Rohaim","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Hala","middleName":"Sedky Gomaa","lastName":"Rohaim","suffix":""},{"id":432412721,"identity":"870d1328-8e08-4012-8f1d-b67f110e9d7a","order_by":3,"name":"Mariam John Amin Ibrahim","email":"data:image/png;base64,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","orcid":"","institution":"Ain Shams University","correspondingAuthor":true,"prefix":"","firstName":"Mariam","middleName":"John Amin","lastName":"Ibrahim","suffix":""}],"badges":[],"createdAt":"2025-01-31 17:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5938163/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5938163/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s43066-026-00493-9","type":"published","date":"2026-01-29T15:59:28+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79319571,"identity":"9877029d-6d5d-4cf6-8890-ea7308d47858","added_by":"auto","created_at":"2025-03-27 04:18:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":28104,"visible":true,"origin":"","legend":"\u003cp\u003econsort of the studied neonates\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5938163/v1/bf05d973203b8ce90ec6bad6.png"},{"id":79319572,"identity":"01521c7c-19dc-43d6-ab94-34cf81ae6685","added_by":"auto","created_at":"2025-03-27 04:18:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":20483,"visible":true,"origin":"","legend":"\u003cp\u003eFollow up of TCB in studied groups\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5938163/v1/4d9fea283a53ca779d56392b.png"},{"id":79319574,"identity":"9722f746-b71c-4586-aa4c-55aa5623b48a","added_by":"auto","created_at":"2025-03-27 04:18:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":19171,"visible":true,"origin":"","legend":"\u003cp\u003eFollow up of TSB in studied groups\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5938163/v1/82152aa6d122b85aa5497877.png"},{"id":101690695,"identity":"bfb1bbbf-28a4-4c27-b7f8-a48b390e527e","added_by":"auto","created_at":"2026-02-02 16:07:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1587124,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5938163/v1/dc16b806-6581-4c74-a4bd-110bad5d32a7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Exploring The Role of Peroxisome Proliferator- Activated Receptor Agonists (Fenofibrate) in Neonatal Jaundice Prevention","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHyperbilirubinemia is a common cause of diagnostic workup and therapeutic intervention in neonates. The prevalence of indirect hyperbilirubinemia (IHB) in term and preterm infants ranges from 60\u0026ndash;90%. The excessive production of bilirubin (as a catabolic product of heme-containing molecules) or reduction in its elimination leads to increased serum bilirubin levels \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFibrates are a class of phenoxy-isobutyric acid derivatives that are peroxisome proliferator-activated alpha receptor agonists. Fibrate, a lipid-lowering drug, can enhance bilirubin conjugation and excretion through induction of uridine diphosphate glucuronosyltransferase \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. Additionally, clofibrate transfers albumin-bound bilirubin to hepatocytes and induces hepatic uptake and conjugation of bilirubin \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. A single dose of fenofibrate (10 mg/kg) as an adjuvant to phototherapy in neonates with hyperbilirubinemia is associated with a significant reduction in serum bilirubin levels \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. Fenofibrate appears to be an effective and safe drug for the treatment of neonatal IHB, consistent with the results of a previous study \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMany neonates are currently diagnosed with neonatal jaundice, either physiological or pathological, with levels reaching the phototherapy threshold and needing neonatal intensive care unit admission due to dehydration from the weather, scanty breast milk, or other benign causes that usually do not elevate the bilirubin level to photo therapy threshold. The use of a preventive drug that helps to decrease bilirubin levels before reaching the phototherapy threshold would be very useful. Therefore, this study aimed to evaluate the preventive role of fenofibrate in term neonates with neonatal jaundice.\u003c/p\u003e"},{"header":"Subjects and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients:\u003c/h2\u003e \u003cp\u003eThe present double-blind controlled clinical trial was performed on 75 full-term neonates with indirect hyperbilirubinemia in the first 10 days after birth. Neonates were observed in the neonatology clinic at Pediatrics Hospital, Ain Shams University Hospital, Cairo, Egypt.\u003c/p\u003e \u003cp\u003eThe inclusion criteria were as follows: full-term neonates(37 to 41 weeks gestational age), appropriate for gestational age, weight between 2500 to3500 gm infants, and indirect hyperbilirubinemia, which was evident on clinical examination and confirmed by transcutaneous and serum bilirubin measurement near but below the level of phototherapy according to the age-specific charts\u003csup\u003e(5)\u003c/sup\u003e ; (neonates were included if the transcutaneous bilirubin was above 12 mg/dl and less than18mg/dl; and were confirmed by total serum bilirubin level measurement before enrollment, measures above this will be indicative for initiation of phototherapy).\u003c/p\u003e \u003cp\u003eInadequate breastfeeding, exaggerated neonatal jaundice, and dehydration were the main causes of indirect hyperbilirubinemia. Hemolytic causes of neonatal hyperbilirubinemia were excluded from the study, this was confirmed by complete blood count, reticulocytic count, direct and indirect combs test and blood group typing for the mother and the neonate (ABO and RH). Newborns with congenital malformations, conjugated hyperbilirubinemia, bilirubin levels reaching exchange transfusion and phototherapy thresholds, ABO or Rh incompatibility, G6PD deficiency, skin abrasions, and infections were excluded.\u003c/p\u003e \u003cp\u003eThe included neonates were divided randomly (closed envelope simple randomization) into three groups: \u003cb\u003esingle dose group\u003c/b\u003e: 25 full-term neonates who received a single oral dose of 10 mg/kg of non-micronized fenofibrate (lipanthyl 300 mg \u0026reg;)diluted in distilled water and an oral dose of equivalent amount of distilled water as a placebo, 24 h a part \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. \u003cb\u003eDouble-dose group\u003c/b\u003e: 25 full-term neonates who received two oral doses of 10 mg/kg of non-micronized fenofibrate diluted in distilled water for 24 h \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. \u003cb\u003eControl group\u003c/b\u003e: 25 full-term neonates gestational age and weight matched to the other groups and who received two oral doses of equivalent amount of distilled water as a placebo 24 h apart. The three groups were examined for adequate breast and artificial feeding and were counselled to perform correctly. The type of feeding (breastfed versus bottle-fed) was matched between the groups to eliminate any potential confounding effect.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMethodology:\u003c/h3\u003e\n\u003cp\u003eAll patients underwent antenatal and natal histories and clinical examinations. Laboratory investigations included Initial Transcutaneous bilirubin levels (TCB) after birth during regular follow-ups. Transcutaneous and serum bilirubin levels were measured before starting the drug or placebo, and then at 12, 24, 36, 48 h, and 5 days after drug intake. Transcutaneous measurements were recorded using a Drager Jaundice Meter JM 105 from the forehead, sternum, and knees. The mean of the three readings was calculated. \u003cb\u003eLaboratory tests done included\u003c/b\u003e: Total serum bilirubin level (TSB) was obtained via venipuncture under aseptic conditions. Serum bile acid was measured initially and 48 h after administration of the drug. Complete blood count, reticulocytic count, direct and indirect combs test and blood group typing for the mother and the neonate (ABO and RH) were done to exclude hemolytic causes of neonatal jaundice. All the patients were followed up for feeding and weight. Participants were sent home and scheduled to visit regularly, as needed in the study.\u003c/p\u003e\n\u003ch3\u003eClinical trials registration:\u003c/h3\u003e\n\u003cp\u003eThis Study was registered on the clinical trials.gov registry number: NCT06451900\u003c/p\u003e \u003cp\u003e \u003cspan class=\"ExternalRef\"\u003e \u003cspan class=\"RefSource\"\u003ehttps://clinicaltrials.gov/study/NCT06451900\u003c/span\u003e \u003cspan address=\"https://clinicaltrials.gov/study/NCT06451900\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e \u003c/span\u003e \u003c/p\u003e\n\u003ch3\u003eSample size calculation:\u003c/h3\u003e\n\u003cp\u003eA sample size of 75 neonates was calculated by using power analysis and sample size software 15 (Version 15.0.10) for sample size calculation, setting power at 80%,at significance level 0.05,using a two-sided two- sample unequal-variance t-test and after reviewing previous study results\u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e showing that the mean serum bilirubin level after 48 hours in neonates with neonatal jaundice who took one dose of fenofibrate was significantly lower than those didn\u0026rsquo;t took fenofibrate(10.05\u0026thinsp;\u0026plusmn;\u0026thinsp;1.58 versus 12.08\u0026thinsp;\u0026plusmn;\u0026thinsp;2.44 respectively ); based on that and after considering 20% drop out rate.\u003c/p\u003e\n\u003ch3\u003eData management and analysis\u003c/h3\u003e\n\u003cp\u003eData were coded, tabulated, and analyzed using the Statistical Package for the Social Sciences version 28 (IBM Corp., Armonk, NY, USA). Data were summarized using mean, standard deviation, median, minimum, and maximum in quantitative data, and frequency (count) and relative frequency (percentage) for qualitative data. To compare categorical data, the chi-square (χ2) test was performed. Exact test was used instead when the expected frequency is less than 5 \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e P-values less than 0.05 were considered as statistically significant\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOne hundred and fifty neonates were evaluated for potential inclusion in the study. Twenty-five were excluded based on the inclusion criteria, while thirty were excluded due to inadequate feeding and weight gain. Nine subjects were lost to follow-up, and eleven did not provide consent (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe demographic and anthropometric measurements of neonates were comparable. Blood group distribution was equivalent among mothers and their neonates, with no statistically significant differences observed between them. Patients in all groups were monitored to assess their feeding patterns, and all were found to maintain consistent feeding modes, with regular bowel movements and adequate, comparable weight gain, thus negating its potential effect on the decrease in bilirubin levels (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison between studied groups regarding anthropometric, demographic data, type of feeding, mode of delivery and blood group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003esingle dose group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDouble dose group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGestational age (weeks)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.220\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWeight (kg)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.024*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (days)**\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(4\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(4\u0026ndash;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(5\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.056\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (44.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (32.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12 (48.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.489\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (56.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (68.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13 (52.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eDelivery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNVD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (84.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e20 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eFeeding\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eArtificial\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.720\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eBreast Milk\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (72.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (84.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e20 (80.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMixed\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (24.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eMaternal blood group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (56.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12 (48.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.896\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (8.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eO\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (36.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (28.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10 (40.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eMaternal Rh\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eRh -ve\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.315\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eRh\u0026thinsp;+\u0026thinsp;ve\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (96.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e22 (88.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eFetal blood group\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (44.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12 (48.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.872\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (8.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eO\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (40.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (32.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e10 (40.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eFetal Rh\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eRh -ve\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.315\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eRh\u0026thinsp;+\u0026thinsp;ve\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (100.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (96.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e22 (88.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eP-values less than 0.05 were considered as statistically significant, *: statistically significant compared to corresponding value in single dose group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), **: median and range#: statistically significant compared to corresponding value in double dose group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), NS: non-significant, S: significant, NVD: normal vaginal delivery, CS: caesarian section.\u003c/p\u003e \u003cp\u003eThe study found that neonates with a double dose of a drug had significantly lower TCB levels at 48 hours compared to those with a single dose, but the difference was not statistically significant (Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe study found a decrease in total systolic blood pressure (TSB) between the studied groups, with the decrease occurring earlier than TCB. Patients in the double-dose group had significantly lower TSB than the control group at 24 hours, 48 hours, and 5 days, and also had lower TSB than the single-dose group at 24 hours, 48 hours, and 5 days \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u0026amp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e), (\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003ePatients in the double-dose group experienced a higher degree of drop in TCB and TSB, with TCB drop occurring at 24, 36, and 48 hours, and TSB drop at 24, 48, and 5 days. \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e \u0026amp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eBile acid levels were significantly lower in the double-dose group before drug intake compared to the single-dose and control groups. \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026amp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison between studied groups regarding TCB, TSB and bile acid levels.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup A (single dose)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup B\u003c/p\u003e \u003cp\u003e(two doses)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup C (Control)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInitial TCB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e15.31\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e15.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e15.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.442\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e12h TCB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e14.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e14.81\u0026thinsp;\u0026plusmn;\u0026thinsp;1.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e14.71\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.922\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e24h TCB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e14.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e13.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e14.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.113\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e36h TCB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e13.28\u0026thinsp;\u0026plusmn;\u0026thinsp;1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e12.65\u0026thinsp;\u0026plusmn;\u0026thinsp;1.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e13.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.077\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e48h TCB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e12.21\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e10.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.11 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e12.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.92 #\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInitial TSB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e14.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e14.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e14.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.581\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e24h TSB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e13.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e12.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e14.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.87 *#\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.002*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e48h TSB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e12.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e11.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72 *#\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e5th day TSB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e8.31\u0026thinsp;\u0026plusmn;\u0026thinsp;1.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.54 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e9.62\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5 *#\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInitial bile acid\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e14.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e13.36\u0026thinsp;\u0026plusmn;\u0026thinsp;1.67 *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e14.89\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53 #\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.003*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e48h bile acid\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e6.53\u0026thinsp;\u0026plusmn;\u0026thinsp;2.03 #\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.004*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eP-values less than 0.05 were considered as statistically significant, TCB: Transcutaneous bilirubin TSB: Total Serum Bilirubin, *: statistically significant compared to corresponding value in Group A (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), #: statistically significant compared to corresponding value in Group B (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), NS: non-significant, S: significant .h: hours\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePost hoc pair wise comparison 48-hour TCB between studied groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup B\u003c/p\u003e \u003cp\u003e(two doses)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup C (Control)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e48h TCB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eGroup A (single dose)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.007*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.643\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eGroup B (two doses)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTCB P-values less than 0.05 were considered as statistically significant, TCB: Transcutaneous.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePost hoc pair wise comparison of TSB between studied groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup B (two doses)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGroup C (Control)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u003cb\u003eTSB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e24h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup A (single dose)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.984\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.032*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup B (two doses)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.002*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e48h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup A (single dose)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.006*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.039*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup B (two doses)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e5 day\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup A (single dose)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.024*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup B (two doses)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTSB P-values less than 0.05 were considered as statistically significant\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePost hoc pair wise comparison of serum bile acid between studied groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup B (two doses)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGroup C (Control)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eBile acid\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eInitial bile acid\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup A (single dose)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.026*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup B (two doses)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.004*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e48h bile acid\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup A (single dose)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.270\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.211\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup B (two doses)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.003*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eP-values less than 0.05 were considered as statistically significant\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDegree of drop of TCB and TSB in studied groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGroup A (single dose)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup B\u003c/p\u003e \u003cp\u003e(two doses)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGroup C (Control)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eTCB % drop\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e12h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.02\u0026thinsp;\u0026plusmn;\u0026thinsp;3.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e6.14\u0026thinsp;\u0026plusmn;\u0026thinsp;2.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e4.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.018\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e24h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.41\u0026thinsp;\u0026plusmn;\u0026thinsp;3.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e12.93\u0026thinsp;\u0026plusmn;\u0026thinsp;4.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e5.49\u0026thinsp;\u0026plusmn;\u0026thinsp;7.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e36h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e13.21\u0026thinsp;\u0026plusmn;\u0026thinsp;4.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e19.79\u0026thinsp;\u0026plusmn;\u0026thinsp;4.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e11.03\u0026thinsp;\u0026plusmn;\u0026thinsp;9.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e48h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e20.19\u0026thinsp;\u0026plusmn;\u0026thinsp;5.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e30.95\u0026thinsp;\u0026plusmn;\u0026thinsp;4.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e15.86\u0026thinsp;\u0026plusmn;\u0026thinsp;13.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eTSB % drop\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e24h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.83\u0026thinsp;\u0026plusmn;\u0026thinsp;3.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e12.69\u0026thinsp;\u0026plusmn;\u0026thinsp;3.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e3.25\u0026thinsp;\u0026plusmn;\u0026thinsp;9.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e48h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e16.46\u0026thinsp;\u0026plusmn;\u0026thinsp;6.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e25.12\u0026thinsp;\u0026plusmn;\u0026thinsp;3.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e21.18\u0026thinsp;\u0026plusmn;\u0026thinsp;31.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e5 day\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e42.63\u0026thinsp;\u0026plusmn;\u0026thinsp;12.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e56.18\u0026thinsp;\u0026plusmn;\u0026thinsp;10.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e47.25\u0026thinsp;\u0026plusmn;\u0026thinsp;28.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eP-values less than 0.05 were considered as statistically significant, TCB: Transcutaneous bilirubin, TSB: Total Serum Bilirubin\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePost hoc pair wise comparison of degree of drop of TCB and TSB between studied Groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGroup B\u003c/p\u003e \u003cp\u003e(two doses)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGroup C (Control)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003e\u003cb\u003eTCB % drop\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e12h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup B\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e----\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e24h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup B\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e----\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e36h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup B\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e----\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e48h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup B\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e----\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e\u003cb\u003eTSB % drop\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e24h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.117\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup B\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e----\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e48h\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup B\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e----\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e5day\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eGroup B\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e----\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eP-values less than 0.05 were considered as statistically significant, TCB: Transcutaneous bilirubin, TSB: Total Serum Bilirubin\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePatients in single and double dose groups B had lower incidences of admission and phototherapy compared to the control group. However, double dose patients had higher drug side effects, including abdominal distension, vomiting, and diarrhea. These issues were managed successfully with minor treatments (Table \u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison between studied groups regarding need for admission, need for phototherapy, incidence of drug side effects, symptoms and signs\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eGroup A (single dose)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eGroup B\u003c/p\u003e \u003cp\u003e(two doses)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eGroup C (Control)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCount\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCount\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCount\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeed admission\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e20.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.009*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReach level of phototherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e20.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.009*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDrug side effects\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e40.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eSymptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eDiarrhea\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.050\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eVomiting\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e80.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e100.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSigns\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAbdominal distension\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.008*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eP-values less than 0.05 were considered as statistically significant, S: significant\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePeroxisome Proliferator-Activated Receptor (PPAR) agonists, such as fenofibrate, have been shown in this study to effectively reduce total serum bilirubin levels with minimal side effects. This suggests a potential protective role in neonates with elevated bilirubin levels near or below phototherapy thresholds. By preventing the rise of serum bilirubin levels, this approach may eliminate the need for NICU admissions for phototherapy and the associated risks.\u003c/p\u003e \u003cp\u003eA drug administered to prevent neonates with elevated serum bilirubin levels from reaching the threshold for phototherapy has not been widely studied. To the best of our knowledge, this study is the first to evaluate the efficacy of fenofibrate as a single prophylactic drug in preventing high serum bilirubin levels in full-term infants not reaching phototherapy levels. Fenofibrate affects bilirubin metabolism by inducing conjugation and excretion of bilirubin \u003csup\u003e(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/sup\u003e. A random sample of 75 full-term babies with hyperbilirubinemia near phototherapy levels was divided into three groups: single-dose, two-dose, and control.\u003c/p\u003e \u003cp\u003eThe neonates in our study demonstrated an early therapeutic response to the administered drug. Those who received a single oral dose exhibited significantly lower total serum bilirubin (TSB) levels compared to the control group at multiple time points: at 24 hours (P\u0026thinsp;=\u0026thinsp;0.032), at 48 hours (P\u0026thinsp;=\u0026thinsp;0.039), and on the fifth day (P\u0026thinsp;=\u0026thinsp;0.024).\u003c/p\u003e \u003cp\u003eSimilarly, previous studies employing a single oral dose of 10 mg/kg of fenofibrate have documented a reduction in TSB levels, primarily in conjunction with phototherapy for the management of neonatal jaundice \u003csup\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/sup\u003e. Consistent with our findings, Al-Banna et al. (2020) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e observed a significant decrease in indirect bilirubin levels in the fenofibrate group at 24, 48, and 72 hours after initiating treatment compared to the control group (P\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eAdditionally, Ahmadpour-Kacho et al. (2018) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e evaluated the effect of oral fenofibrate on TSB levels in term neonates with initial bilirubin levels exceeding 15 mg/dL. Their results showed a significant reduction in TSB levels in the intervention group compared to controls at 48 hours and on the third day of hospitalization.\u003c/p\u003e \u003cp\u003eIn contrast, the study by Prabha and Saravanan (2020) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e reported a decline in TSB levels after 48 hours of phototherapy combined with fenofibrate; however, the difference between the fenofibrate and control groups was not statistically significant. However, it is important to note that in all the aforementioned studies, fenofibrate was used in conjunction with phototherapy, making it difficult to isolate the independent effect of fenofibrate on bilirubin levels. In contrast, our study successfully delineates the specific impact of fenofibrate in neonates with hyperbilirubinemia, as the intervention was administered without the confounding influence of phototherapy.\u003c/p\u003e \u003cp\u003eNeonates in the double-dose group in our study demonstrated a significant and prolonged effect of the drug, evidenced by reduced total serum bilirubin (TSB) levels at both 48 hours and five days following administration. In contrast, Awad et al. (2021) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e reported no statistically significant difference in the decline of TSB between neonates receiving a single dose of fenofibrate and those receiving a double dose at 12, 24-, 36-, 48-, or 72-hours post-intervention. Upon reviewing the literature, our study and that of Awad et al. (2021) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e appear to be the only investigations evaluating the use of a double dose of fenofibrate in managing neonatal unconjugated hyperbilirubinemia. However, Awad et al. (2021) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e emphasized that their findings comparing single- and double-dose regimens should be interpreted cautiously, as their study was not sufficiently powered to detect differences in efficacy.\u003c/p\u003e \u003cp\u003eAccording to our findings, neonates in both the single- and double-dose groups required significantly fewer hospital admissions and phototherapy sessions compared to the control group (P\u0026thinsp;=\u0026thinsp;0.009), reinforcing the potential of fenofibrate to effectively reduce bilirubin levels. Supporting our findings, Abdellatif et al. (2023) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e conducted a meta-analysis that demonstrated fenofibrate combined with phototherapy significantly reduced the duration of phototherapy and hospital stay. They concluded that fenofibrate may serve as a safe adjunct to neonatal phototherapy. Additionally, Awad et al. (2021) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e found that fenofibrate administration, irrespective of the dosage, was associated with a shorter duration of phototherapy and hospital stay compared to phototherapy alone. They concluded that fenofibrate is well-tolerated and associated with significant reductions in serum bilirubin, phototherapy duration, and hospital stay, with no significant adverse effects. Similarly, other studies have documented a reduction in phototherapy duration and hospital stay associated with fenofibrate use \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e Nonetheless, further large-scale randomized controlled trials are warranted to confirm these findings.\u003c/p\u003e \u003cp\u003eIn contrast, Saadat et al. (2023) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e reported no statistically significant reduction in hospital length of stay between the fenofibrate and control groups (P\u0026thinsp;=\u0026thinsp;0.612). Likewise, Prabha and Saravanan (2020) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e observed a decrease in phototherapy duration in the intervention group, but the difference was not statistically significant.\u003c/p\u003e \u003cp\u003eRegarding safety, neonates in the double-dose group in our study experienced a higher incidence of drug-related side effects, including abdominal distension, compared to the single-dose and control groups. However, the reported adverse effects, such as diarrhea (two episodes per day) and vomiting (once per day), were mild, did not lead to dehydration, and did not affect the infants\u0026rsquo; weight or general condition. Based on these observations, we conclude that fenofibrate is well-tolerated, with side effects that are manageable and clinically insignificant. Consistent with our findings, Awad et al. (2021) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e reported no statistically significant differences in adverse effects across all studied groups. Additionally, Chaudhary et al. (2016) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e observed no side effects following a single-dose administration of fenofibrate.\u003c/p\u003e \u003cp\u003eThe majority of prior studies have focused on the use of fenofibrate in neonates with confirmed hyperbilirubinemia requiring intervention. However, the results of our study suggest that fenofibrate may also have a prophylactic role in managing hyperbilirubinemia. Neonates at risk of developing hyperbilirubinemia due to factors such as scanty breastfeeding, dehydration, breast milk jaundice, or breastfeeding jaundice could benefit from fenofibrate, potentially reducing the need for hospital admission.\u003c/p\u003e\n\u003ch3\u003eLimitations of the study\u003c/h3\u003e\n\u003cp\u003eDespite the optimized benefits demonstrated in this study regarding the effectiveness of fenofibrate in reducing serum bilirubin levels in neonates, it is important to acknowledge that this remains an experimental trial. Further large-scale studies are recommended to validate these findings and ensure their clinical applicability.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFenofibrate, when used as a prophylactic therapy in full-term neonates with elevated bilirubin levels approaching the threshold for phototherapy, was found to be well-tolerated and effective. Its use was associated with a significant reduction in serum bilirubin levels, as well as a decreased need for phototherapy and hospital admission. Moreover, double-dose fenofibrate demonstrated a greater reduction in total serum bilirubin compared to the single-dose regimen, without a significant increase in adverse effects.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eTCB: Transcutaneous bilirubin\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTSB Total serum bilirubin\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIHB: Indirect hyperbilirubinemia\u003c/p\u003e\n\u003cp\u003eRh: Rhesus factor\u003c/p\u003e\n\u003cp\u003eG6PD: glucose 6 phosphate dehydrogenase\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eApproval of the Research Ethics Committee of faculty of medicine Ain Shams University was obtained before the start of the research (MS 383/2023). An informed written consent was obtained from the parents or guardians of the patients or controls before inclusion in the study. Data collected was strictly confidential and only used for research purposes. The participants had the right to drop from the trial at any time they requested. Personal data of the participants were not used in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. Personal data of the participants were not used in the study.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was obtained for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNA and RA provided the idea and design of the study. \u0026nbsp;NA, RA, HR and MI wrote and revised the study protocol. HR was involved in the recruitment of patients, intervention, data collection, and follow-up. NA, HR, RA and MI performed the data analysis and interpretation, wrote the manuscript and revised it. All the authors reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to the thank all the participants in the trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eRania Mohamed Abdo:\u0026nbsp;\u003cul style=\"list-style-type: circle;\"\u003e\n \u003cli\u003eAssistant Professor of Pediatrics and Neonatology, Faculty of Medicine, Ain Shams University, Cairo, Egypt\u003c/li\u003e\n \u003cli\[email protected]\u003c/li\u003e\n \u003cli\u003eOrcid no: 0000-0003-4799-1377\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eHala Sedky Gomaa Rohaim :\u0026nbsp;\u003cul style=\"list-style-type: circle;\"\u003e\n \u003cli\u003ePediatric resident in ministry of health and population, Egypt,\u003c/li\u003e\n \u003cli\[email protected]\u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eNancy Mohamed Abo Shady:\u0026nbsp;\u003cul style=\"list-style-type: circle;\"\u003e\n \u003cli\u003eProfessor of pediatrics and neonatology, Faculty of Medicine, Ain Shams University.\u003c/li\u003e\n \u003cli\[email protected]\u0026nbsp;\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eMariam John Amin Ibrahim:\u0026nbsp;\u003cul style=\"list-style-type: circle;\"\u003e\n \u003cli\u003eAssistant Professor of Pediatrics and Neonatology, Faculty of Medicine, Ain Shams University, Cairo, Egypt\u003c/li\u003e\n \u003cli\[email protected],\u003c/li\u003e\n \u003cli\u003eORCID number: 0000-0002-4936-8303\u003c/li\u003e\n \u003cli\u003eTel: +201224357701\u003c/li\u003e\n \u003cli\u003eCorresponding author\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHansen TWR, Maisels MJ, Ebbesen F, Vreman HJ, Stevenson DK, Wong RJ, et al. (2020) Sixty years of phototherapy for neonatal jaundice \u0026ndash; from serendipitous observation to standardized treatment and rescue for millions. J Perinatol.;40(2):180-93.\u003c/li\u003e\n\u003cli\u003eChaudhary, G. S., Chaudhary, V., Chaurasiya, O. S., Chandrakant, V., \u0026amp; Kumar, V. (2016). Oral fenofibrate in neonatal hyperbilirubinemia: A randomized controlled trial. Indian Journal of Child Health, 54-58. \u003c/li\u003e\n\u003cli\u003eKhafaga, K. A., Alsaid, L. M., Salama, R. H., \u0026amp; Abougabal, M. T. (2022). Fenofibrate As an Adjuvant to Phototherapy in Term Neonates with Hyperbilirubinemia; A Randomized Controlled Clinical Trial. The Egyptian Journal of Hospital Medicine, 89(1), 4439-4443.\u003c/li\u003e\n\u003cli\u003eEghbalian F, Hasanpour-Dehkordi A, Raeisi R. ( 2022) The Effects of Clofibrate on Neonatal Jaundice: A Systematic Review. Int J Prev Med.;13:3.\u003c/li\u003e\n\u003cli\u003eKemper AR, Newman TB, Slaughter JL, et al, for the American Academy of Pediatrics. Clinical practice guideline revision: Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2022 Aug 5:e2022058859. PMID: 35927462.\u003c/li\u003e\n\u003cli\u003eChan YH (2003): Biostatistics 103: Qualitative Data \u0026ndash;Tests of Independence. Singapore Med J.;44(10): 498-503.\u003c/li\u003e\n\u003cli\u003eShabo, S. K., Gargary, K. H., \u0026amp; Erdeve, O. (2023). Indirect Neonatal Hyperbilirubinemia and the Role of Fenofibrate as an Adjuvant to Phototherapy. Children, 10(7), 1192.\u003c/li\u003e\n\u003cli\u003eSaadat, S. H., Goodarzi, R., \u0026amp; Gharaei, B. (2023). Oral fenofibrate for hyperbilirubinemia in term neonates: A single-blind randomized controlled trial. Journal of Clinical and Translational Science, 7(1), e85.\u003c/li\u003e\n\u003cli\u003eAwad, M. H., Amer, S., Hafez, M., Nour, I., \u0026amp; Shabaan, A. (2021). Fenofibrate as an adjuvant to phototherapy in pathological unconjugated hyperbilirubinemia in neonates: a randomized control trial. Journal of Perinatology, 41(4), 865-872.\u003c/li\u003e\n\u003cli\u003eAl-Banna, S. M., Riad, A. N., \u0026amp; Anis, S. S. (2020). The effect of fenofibrate and antioxidant vitamins [D, E and C] in treatment of uncomplicated neonatal hyperbilirubinemia. Annals of Neonatology Journal, 2(1), 37-48.\u003c/li\u003e\n\u003cli\u003eAhmadpour-kacho, M., Zahed Pasha, Y., Moghadamnia, A. A., Khafri, S., \u0026amp; Vafaeinezhad, M. (2018). The effect of oral fenofibrate on serum bilirubin level in term neonates with hyperbilirubinemia: a randomized clinical trail. International Journal of Pediatrics, 6(10), 8317-8327.\u003c/li\u003e\n\u003cli\u003ePrabha, M. S., \u0026amp; Saravanan, S. (2020). The efficacy of fenofibrate as an adjunct to phototherapy for neonatal hyperbilirubinemia. International Journal of Pediatrics and Geriatrics, 3(2), 73-75.\u003c/li\u003e\n\u003cli\u003eAbdellatif, M., Abozaid, A. A. F., Shah, P. S., Dhouibi, N., Nguyen-Khac, T., Khleif, R., ... \u0026amp; Huy, N. T. (2023). Efficacy and safety of fenofibrate in combination with phototherapy for the treatment of neonatal hyperbilirubinemia: a systematic review and meta-analyses. Canadian Journal of Physiology and Pharmacology.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"full term neonate, neonate, neonatal jaundice, indirect hyperbilirubinemia, fenofibrate, peroxisome proliferator","lastPublishedDoi":"10.21203/rs.3.rs-5938163/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5938163/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Neonatal jaundice is one of the most prevalent illnesses in neonates, requiring care and treatment. Fenofibrate is a lipid-lowering drug that enhances the conjugation and excretion of bilirubin. Previous studies have suggested the usefulness of fenofibrate for the treatment of indirect hyperbilirubinemia in neonates.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e To evaluate the role of fenofibrate in neonates with neonatal jaundice near the level of phototherapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients and Methods: \u003c/strong\u003eseventy- five full-term infants with neonatal jaundice near the level of phototherapy were randomly divided into three groups:\u003cstrong\u003e single-dose group:\u003c/strong\u003e 25 neonates received a single oral dose of 10 mg/kg of non-micronized fenofibrate and an oral dose of an equivalent amount of distilled water as a placebo\u003cstrong\u003e. Double-dose group:\u003c/strong\u003e 25 neonates received two oral doses of 10 mg/kg non-micronized fenofibrate. \u003cstrong\u003eThe control group included\u003c/strong\u003e 25 neonates who received two oral doses of an equivalent amount of distilled water as a placebo.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003cem\u003e\u003cstrong\u003e \u003c/strong\u003e\u003c/em\u003eThe double-dose group had the highest significant drop in transcutaneous bilirubin (TCB) starting from 12 to 48 h after drug intake and the highest drop in total serum bilirubin (TSB) starting from 12 h to the 5\u003csup\u003eth\u003c/sup\u003e day in comparison to the single-dose group and the controls. The single-dose and double-dose groups had a significantly lower incidence of the need for admission and phototherapy than the control group (P=0.009). The double-dose group had a significantly higher incidence of drug side effects than the single-dose group (P\u0026lt; 0.001), mainly in the form of abdominal distension (P=0.008); however, only minor treatment was required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eFenofibrate can significantly decrease bilirubin levels in full-term neonates with neonatal jaundice near the level of phototherapy, with no need for admission and phototherapy management. The drug was well-tolerated and safe. Double-dose treatment with fenofibrate significantly lowered TSB with no significant increase in side effects when compared to the single-dose group.\u003c/p\u003e","manuscriptTitle":"Exploring The Role of Peroxisome Proliferator- Activated Receptor Agonists (Fenofibrate) in Neonatal Jaundice Prevention","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-27 04:18:50","doi":"10.21203/rs.3.rs-5938163/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c150c51d-7570-4737-9c0e-a6fb35d0309b","owner":[],"postedDate":"March 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-02T16:03:56+00:00","versionOfRecord":{"articleIdentity":"rs-5938163","link":"https://doi.org/10.1186/s43066-026-00493-9","journal":{"identity":"egyptian-liver-journal","isVorOnly":false,"title":"Egyptian Liver Journal"},"publishedOn":"2026-01-29 15:59:28","publishedOnDateReadable":"January 29th, 2026"},"versionCreatedAt":"2025-03-27 04:18:50","video":"","vorDoi":"10.1186/s43066-026-00493-9","vorDoiUrl":"https://doi.org/10.1186/s43066-026-00493-9","workflowStages":[]},"version":"v1","identity":"rs-5938163","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5938163","identity":"rs-5938163","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}