Intravenous immunoglobulin G therapy for neonatal hyperbilirubinemia.

BACKGROUND: Neonatal hyperbilirubinemia (NHb) results from increased total serum bilirubin and is a common reason for admission and readmission amongst newborn infants born in North America. The use of intravenous immunoglobulin (IVIG) therapy for treating NHb has been widely debated, and the current incidence of NHb and its therapies remain unknown. METHODS: Using national and provincial databases, a population-based retrospective cohort study of infants born in Ontario from April 2014 to March 2018 was conducted. RESULTS: Of the 533,084 infants born in Ontario at ≥35 weeks gestation, 29,756 (5.6%) presented with NHb. Among these infants, 80.1-88.2% received phototherapy, 1.1-2.0% received IVIG therapy and 0.1-0.2% received exchange transfusion (ET) over the study period. Although phototherapy was administered (83.0%) for NHb, its use decreased from 2014 to 2018 (88.2-80.1%) (P < 0.01). Similarly, the incidence of IVIG therapy increased from 71 to 156 infants (1.1-2.0%) (P < 0.01) and a small change in the incidence of ET (0.2-0.1%) was noted. CONCLUSION: IVIG therapy is increasingly being used in Ontario despite limited studies evaluating its use. The results of this study could inform treatment and management protocols for NHb. IMPACTS: Clinically significant neonatal hyperbilirubinemia still occurs in Ontario, with an increasing number of infants receiving Intravenous Immunoglobulin G (IVIG) therapy. IVIG continues to be used at increasing rates despite inconclusive evidence to recommend its use. This study highlights the necessity of a future prospective study to better determine the effectiveness of IVIG use in treating neonatal hyperbilirubinemia, especially given the recent shortage in IVIG supply in Ontario. The results of this study could inform treatment and management protocols for neonatal hyperbilirubinemia.

Role of ursodeoxycholic acid in neonatal indirect hyperbilirubinemia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Neonatal jaundice is a transitional phenomenon affecting three out of five full-term newborns globally. Ursodeoxycholic acid could be beneficial in neonatal jaundice needing phototherapy.  METHODS: We searched PubMed, EBSCO, ProQuest, and Cochrane Library up to August 21st, 2021, for articles to be reviewed. Meta-analysis using random-effects model was performed. RESULTS: Eight studies involving 1116 neonates were chosen in this review; however, only five studies were included for meta-analysis. Phototherapy duration was significantly lower in the interventional group with high heterogeneities. Subgroup analysis of the phototherapy duration based on the risk of bias resulted in a shorter duration (mean difference (MD) = -17.82; 95% CI = -20.17 to -15.47; p = < 0.001) with low heterogeneity in the treatment group. Secondary outcome focusing on mean total serum bilirubin showed a lower mean total serum bilirubin in 48 h post-treatment (MD = -0.43; 95% CI = -0.64 to -0.22; p = < 0.0001) with low heterogeneities in Asian countries." CONCLUSIONS: Ursodeoxycholic acid might be considered as a novel adjuvant therapy in neonatal indirect hyperbilirubinemia to shorten the phototherapy duration and lower the mean total serum bilirubin.

Potential of therapeutic bile acids in the treatment of neonatal Hyperbilirubinemia.

Neonatal hyperbilirubinemia or jaundice is associated with kernicterus, resulting in permanent neurological damage or even death. Conventional phototherapy does not prevent hyperbilirubinemia or eliminate the need for exchange transfusion. Here we investigated the potential of therapeutic bile acids ursodeoxycholic acid (UDCA) and obeticholic acid (OCA, 6-α-ethyl-CDCA), a farnesoid-X-receptor (FXR) agonist, as preventive treatment options for neonatal hyperbilirubinemia using the hUGT1*1 humanized mice and Ugt1a-deficient Gunn rats. Treatment of hUGT1*1 mice with UDCA or OCA at postnatal days 10-14 effectively decreased bilirubin in plasma (by 82% and 62%) and brain (by 72% and 69%), respectively. Mechanistically, our findings indicate that these effects are mediated through induction of protein levels of hUGT1A1 in the intestine, but not in liver. We further demonstrate that in Ugt1a-deficient Gunn rats, UDCA but not OCA significantly decreases plasma bilirubin, indicating that at least some of the hypobilirubinemic effects of UDCA are independent of UGT1A1. Finally, using the synthetic, non-bile acid, FXR-agonist GW4064, we show that some of these effects are mediated through direct or indirect activation of FXR. Together, our study shows that therapeutic bile acids UDCA and OCA effectively reduce both plasma and brain bilirubin, highlighting their potential in the treatment of neonatal hyperbilirubinemia.

Evaluating the effect of ursodeoxycholic acid on total bilirubin of neonates with glucose-6-phosphate dehydrogenase deficiency complicated by indirect hyperbilirubinaemia.

AIM: This study aimed to investigate the effect of adding ursodeoxycholic acid (UDCA) to phototherapy in neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency and hyperbilirubinaemia. G6PD deficiency is a common cause of severe hyperbilirubinaemia in neonates. METHODS: This study was a triple blind, clinical trial study of 40 neonates with G6PD deficiency and hyperbilirubinaemia who admitted for phototherapy in hospitals affiliated to the University of Medical Sciences. The treatment group (n = 20) received UDCA 10 mg/kg (2 cc/kg) daily divided into 2 doses every 12 h. The control group (n = 20) received the same volume of placebo syrup. The drug and placebo treatments were continued until the bilirubin level dropped below 171 µmol/L. Both the control and treatment group received continuous phototherapy. Independent sample t-test, survival analysis and logrank test were used to statistically analyse the results. RESULTS: The mean total bilirubin level was 231.9 ± 18.8 µmol/L and 184.3 ± 18.6 µmol/L in the control and intervention group respectively, 24 h after drug administration and 209.7 ± 19.3 µmol/L and 157.4 ± 16.4 µmol/L, respectively, 48 h after intervention (P < 0.05). The median length of hospitalisation in the treatment group was approximately 1 day lower than the control group (logrank test P value: <0.001). CONCLUSION: The study showed that the addition of UDCA to phototherapy accelerates the reduction of total bilirubin level in neonates with G6PD deficiency and can reduce the duration of hospitalisation.

Efficacy of zinc sulfate on indirect hyperbilirubinemia in premature infants admitted to neonatal intensive care unit: a double-blind, randomized clinical trial.

BACKGROUND: Hyperbilirubinemia is a common neonatal problem. Studies conducted on the effectiveness of zinc salts on serum indirect bilirubin levels in newborns have yielded different results, all calling for further research. This study aimed to determine the effect of oral zinc sulfate on indirect hyperbilirubinemia in preterm infants admitted to the neonatal intensive care unit. METHODS: A randomized double-blind clinical trial was performed in the neonatal intensive care unit of Vali-e-Asr Hospital in Birjand, Iran. The study population comprised neonates aged between 31 and 36 gestational weeks, who required phototherapy in the neonatal intensive care unit. A total of 60 neonates were selected by census and allocated into an experimental group and a control group. In addition to phototherapy, the experimental group received 1 cc/Kg zinc sulfate syrup (containing 5 mg/5 cc zinc sulfate; Merck Company, Germany), and the control group received a placebo syrup (containing 1 cc/kg sucrose). Data were analyzed in SPSS-21 software using the independent t-test, repeated-measures ANOVA, Bonferroni post-hoc test, and Mann-Whitney test. P-values smaller than 0.05 were considered significant. RESULTS: Bilirubin level changes in the experimental and control groups six hours after intervention were - 1.45 ± 3.23 and - 0.49 ± 0.37 (p = 0.024), respectively. The changes 24 and 48 h after intervention were-3.26 ± 2.78 and - 1.89 ± 1.20 (p = 0.017) in the experimental group and - 4.89 ± 2.76 and - 3.98 ± 2.32 (p = 0.23) in the control group, respectively. There was no significant difference in the phototherapy duration between the two groups (p = 0.24). CONCLUSIONS: The results of this study showed that the use of zinc sulfate syrup in preterm infants with indirect hyperbilirubinemia significantly reduced bilirubin levels within 48 h of treatment. TRIAL REGISTRATION: Trial registration: IRCT, IRCT2015120825439N1. Registered 21 February 2016, http://irct.ir/trial/21277.

Clofibrate as an Adjunct to Phototherapy for Unconjugated Hyperbilirubinemia in Term Neonates.

OBJECTIVE: To evaluate the efficacy of oral clofibrate as an adjunct to phototherapy for unconjugated hyperbilirubinemia in term neonates. METHODS: This randomized controlled trial was done in the level III neonatal intensive care unit (NICU) of a tertiary care hospital. Ninety term neonates with unconjugated hyperbilirubinemia with serum bilirubin 15-25 mg/dl were randomized to either intervention group (single dose of clofibrate in a dose of 50 mg/kg prior to starting phototherapy) or standard care group (only phototherapy). Primary outcome was absolute fall in bilirubin by 48 h. Secondary outcomes were duration of phototherapy, absolute fall in bilirubin levels at 12, 24, 36, 48 h, need for exchange transfusion and incidence of side-effects. RESULTS: After 48 h of intervention, significantly lower bilirubin levels were noted in the intervention group compared to standard care group with a mean difference of 7 mg/dl (95% CI 6.7 mg/dl to 7.2 mg/dl). Duration of phototherapy required was less in the intervention group compared to standard care group with mean difference of 23.82 h (95% CI 30.46 h to 17.18 h). Exchange transfusion was needed for 4 neonates in the standard care group and none in the intervention group. No side-effects were noted with clofibrate. CONCLUSIONS: Single dose clofibrate prior to starting phototherapy in term neonates with uncomplicated unconjugated hyperbilirubinemia reduces the duration of phototherapy significantly.

Yinzhihuang oral liquid in the treatment of neonatal jaundice: a meta-analysis.

CONTEXT: Yinzhihuang oral liquid, a well-known Chinese herbal formula, is a clinical drug for the treatment of neonatal jaundice, and a number of clinical trials have been published addressing this issue, but there is no comprehensive analysis that evaluates its efficacy for the treatment of newborn with hyperbilirubinaemia. OBJECTIVE: A meta-analysis was conducted to evaluate the efficacy of Yinzhihuang oral liquid on neonatal jaundice. METHODS: Search was performed throughout PubMed, Cochrane Library, EMBASE, Ovid, Wanfang, VIP Medicine Information System (VMIS) and China National Knowledge Infrastructure (CNKI) databases up to December 2015. The search terms were (Yinzhihuang oral liquid or Yinzhihuang oral solution), (neonatal jaundice or neonatal hyperbilirubinaemia), and (efficacy). Review Manager 5.2 software was used for analyzing the data. Data were pooled by using the random-effects models and expressed as relative ratio (RR), standardized mean difference (SMD) or mean difference (MD) with a 95% confidence interval (CI). The Cochrane tool was applied to assess the risk of bias of the trials. RESULTS: Yinzhihuang oral liquid in conjunction with other therapy increased effective rate of neonatal jaundice therapy (RR =1.14, 95%CI: 1.08-1.20). Yinzhihuang oral liquid significantly eliminated overproduced bilirubin which was measured by TSB or TCB at the third day and fifth day during the treatment {[third day, SMD = -1.63, 95%CI: -2.20 to (-1.06)], [fifth day, SMD = -5.00, 95%CI: -7.88 to (-2.12)]}; Yinzhihuang oral liquid significantly shortened jaundice subsiding time [MD = -3.20, 95%CI: -6.01to (-0.39)]. CONCLUSION: Yinzhihuang oral liquid can be considered as an effective treatment option for neonatal jaundice.

Zinc supplementation for neonatal hyperbilirubinemia: a randomized controlled trial.

OBJECTIVE: To determine the efficacy of oral zinc for treatment of idiopathic neonatal hyperbilirubinemia in near-term and term (35-41 weeks) neonates. DESIGN: Randomized placebo-controlled trial. SETTING: Tertiary-care teaching hospital. PARTICIPANTS: Eighty newborns with idiopathic neonatal hyperbilirubinemia. INTERVENTION: Neonates were randomized to receive either oral zinc sulfate (10 mg/d) or placebo for 7 days. MAIN OUTCOME MEASURES: Primary: total serum bilirubin levels at 48 (±12) h, 96 (±12) h and 144 (±12) h after intervention. Secondary: duration of phototherapy, and serum zinc and copper levels. RESULTS: Baseline mean (SD) total serum bilirubin levels were 14.8 (3.8) and 14.4 (3.5) mg/dL in zinc and placebo groups, respectively. No significant differences were observed in total bilirubin levels between the two groups after the intervention. Mean (SD) total serum bilirubin levels in zinc and placebo groups were 13.9 (2.5) vs. 13.4 (1.9) mg/dL (mean difference 0.566; 95% CI -0.535, 1.668, P=0.038) at 48 h, 13.1 (2.7) vs. 12.8 (2.3) mg/dL (mean difference 0.234; 95% CI -1.011, 1.479, P =0.708) at 96 h and 8.0 (2.0) vs. 8.6 (1.2) mg/dL (mean difference -0.569, 95% CI -1.382, 0.242, P=0.166) at 144 h. Although the mean duration of phototherapy in the zinc group was less by 21.3 h (95% CI 11.6, 30.9, P=0.052), the difference was not significant. Post-intervention, serum zinc levels were significantly higher in the zinc-supplemented group while serum copper levels were comparable between the two groups. CONCLUSIONS: Oral zinc sulfate, in a dose of 10 mg/day, is not effective in the management of idiopathic neonatal hyperbilirubinemia.

Evaluation of safety and efficacy of purgative manna (billinaster drop) and glycerin suppository in icterus of healthy term newborns.

OBJECTIVE: The aim of the present study was to investigate safety and efficacy of billinaster drop and glycerin suppository in hyperbilirubinemia of healthy term newborns who had passage of first meconium. METHODS: In a randomized clinical trial, 90 neonates with total plasma bilirubin(TPB) level of 15-20mg/dL, were randomly assigned to be treated with alone phototherapy (control) or 5drop/kg of bilinaster drop every eight hours and phototherapy(B) or half of glycerin suppository every twelve hours and phototherapy(G). The primary outcomes were safety of drugs and efficacy in obtaining TPB of less than 14 mg/dL as measured at the beginning, 12, 24 and 48 hours after intervention. Secondary endpoint was hospitalization days. RESULTS: After 48 hours of intervention, achieving TPB of less than 14 mg/dL was seen in 50 %( N=15) in control group, 73.3 %( N=22) in B group and 86.7 %( N=26 neonates) in G group (P= 0.01). Watery stool was seen in two neonates of glycerin group and safety of the treatments was not significantly different. Mean of TPB 12 hours after beginning of phototherapy(mean±SD:14.38±2.27mg/dL in G, 15.97±1.96mg/dL in B and 16.67±1.77mg/dL in control), 24 hours after intervention(mean±SD:12.56 ±1.59mg/dL in G, 12.57±2.05mg/dL in B and 14.36±2.26mg/dL in control), 48 hours after intervention (mean±SD: 9.34 ± 1.6mg/dL in G, 9.96 ± 2.95mg/dL in B and 12.27 ± 2.4mg/dL in control) and mean of hospitalization days (mean± SD: 1.5 ± 0.4days in G, 1.7 ± 0.4days in B and 2.9 ± 1.1days in control) were significantly lower in glycerin and billinaster groups. CONCLUSION: Bilinaster drop and glycerin suppository can be used as hazardless, efficient and cost effective drugs in treatment of neonatal hyperbilirubinemia.

Effect of light exposure on metalloporphyrin-treated newborn mice.

BACKGROUND: Neonatal hyperbilirubinemia arises from increased bilirubin production and decreased bilirubin elimination. Although phototherapy safely and effectively reduces bilirubin levels, recent evidence shows that it has adverse effects. Therefore, alternative treatments are warranted. Metalloporphyrins, competitive inhibitors of heme oxygenase (HO), the rate-limiting enzyme in bilirubin production, effectively reduce bilirubin formation; however, many are photoreactive. Here, we investigated possible photosensitizing effects of chromium mesoporphyrin (CrMP) and zinc deuteroporphyrin bis-glycol (ZnBG). METHODS AND RESULTS: Administration of CrMP or ZnBG to 3-d-old mouse pups (3.75-30.0 µmol/kg intraperitoneally) and exposure to cool white (F20T12CW) and blue (TL20W/52) fluorescent lights (+L) for 3 h, resulted in a dose-dependent mortality (50% lethal dose (LD50) = 21.5 and 19.5 µmol/kg, respectively). In contrast to ZnBG, there was no significant difference in survival between the CrMP+L and CrMP groups. Following 30 µmol/kg ZnBG+L, we found significant weight loss, decreased liver antioxidant capacities, and increased aspartate aminotransaminase levels. At 6-d post-light exposure, ZnBG+L-treated pups showed gross and histologic skin changes at doses >7.5 µmol/kg. No lethality was observed following treatment with 30 µmol ZnBG/kg plus exposure to blue light-emitting diodes. Phototoxicity of ZnBG was dependent on light source, emission spectrum, and irradiance. CONCLUSION: Low doses of ZnBG (<3.75 µmol/kg) retained maximal HO inhibitory potency without photosensitizing effects, and therefore are potentially useful in treating neonatal hyperbilirubinemia.

Clofibrate for unconjugated hyperbilirubinemia in neonates: a systematic review.

OBJECTIVE: To evaluate the effect of clofibrate for unconjugated hyperbilirubinemia in neonates. METHODS: A systematic review with meta-analysis of randomized controlled trials or quasi-randomized controlled trials was conducted to evaluate the clofibrate treatment in neonates with unconjugated hyperbilirubinemia. We followed the guidelines from the Cochrane review group and the PRISMA statement. RESULTS: Of 148 studies identified, a total of 13 studies on 867 infants were included. A single oral administration of clofibrate was associated with decreased need of phototherapy (RR:.38, 95% CI: 0.21 to 0.68), shortened duration of phototherapy (mean duration: 23.88 h, 95% CI: 33.03 to -14.72 h) and reduced peak total serum bilirubin (mean duration: -1.62 mg/dL, 95% CI: 2.13 to -1.11 mg/dL). These effects were especially obvious in term infants and infants without hemolytic diseases. Data regarding mortality or kernicterus were not available from included studies. CONCLUSIONS: Clofibrate may have short-term benefits for the infants with hyperbilirubinaemia, especially for population of term infants and infants without hemolytic diseases. Large RCTs with long-term followup are required to verify the safety of clofibrate and assess its long-term effects.

The effect of clofibrate on hyperbilirubinemia of term neonates.

Clofibrate is a glucuronosyl transferase inducer that has been proposed to increase the elimination of bilirubin in neonates with hyperbilirubinemia. This study was conducted to determine the therapeutic effect of clofibrate in term neonates with non-hemolytic jaundice. This study was conducted on 52 newborns with pathologic unconjugated jaundice in Qazvin children hospital. Newborns divided randomly in two groups. Case group treated with clofibrate and intensive phototherapy, while control group treated only with intensive phototherapy. Serum bilirubin level was measured before and 6, 12, 24 and 48 hours after treatment. Results were compared and analyzed. The mean serum level of bilirubin before treatment in the case and control groups were 20.78 ± 2.38 and 20.52 ± 2.44 mg/dl, respectively (P=0.69). The mean serum level of bilirubin in 6, 12, 24 and 48 hours after treatment in the case group were 18.20 ± 2.20, 14.70 ± 2.06, 10.72 ± 2.40 and 8.90 ± 0.83 mg/dl , respectively. These values in control group were 18.26 ± 2.42, 15.36 ± 2.59, 12.29 ± 2.28 and 10.23 ± 1.50 mg/dl, respectively. There was significant difference between two groups regarding mean serum level of bilirubin 24 hours (P=0.019) and 48 hours after treatment (P=0.005). In conclusion, clofibrate was effective in reducing neonatal jaundice and its effect appeared 24 hours after treatment.

[A multicenter randomized controlled study on the efficacy and safety of Yinzhihuang oral solution for the treatment of neonatal indirect hyperbilirubinemia in term newborn infants].

OBJECTIVE: A large-scale prospective multicenter randomized controlled trial was conducted to evaluate the efficacy and safety of Yinzhihuang oral solution for the treatment of neonatal indirect hyperbilirubinemia in term newborn infants. Yinzhihuang oral solution is a herbal extract with the main components of Herba Artemisiae Scopariae, Scutellaria, Lonicera Japonica and Gardenia jasminoides. METHODS: A total of 16 hospitals participated in this study. From March to September 2010, the term infants whose bilirubin level ≥ 40 th percentile for age in hours were enrolled, except for those who received exchange transfusion or had signs of bilirubin encephalopathy. All the 1177 cases were divided randomly into three groups: phototherapy group (409 cases), phenobarbital combined with phototherapy group (373 cases) and Yinzhihuang oral liquid combined with phototherapy group (395 cases). Phenobarbital and Yinzhihuang oral liquid was started once the infants participated the study, and persisted for 5 days. Phototherapy was added as soon as the bilirubin level reached the lowest threshold (the threshold for infants at higher risk). The demographic data of infants in each group were recorded, the serum bilirubin level before treatment, after treatment for 72 hours and after the treatment completion were checked. The reduction rate of serum bilirubin and the phototherapy rate in different groups were compared. The adverse events were assessed as well. RESULTS: Of the total of 1177 cases, 707 (60.1%) were male, 1119 cases (95.1%) were of Han ethnicity. The average total bilirubin level before treatment was (282.0 ± 70.9) µmol/L and the highest level was 626 µmol/L. The severe hyperbilirubinemia (total bilirubin level at 342 µmol/L to 427 µmol/L) accounted for 15.8% (186 cases), and the extremely severe hyperbilirubinemia (total bilirubin > 427 µmol/L) accounted for 2.5% (30 cases). After treatment for 72 hours, the reduction of bilirubin was not significantly different among three groups (F = 2.89, P = 0.056). After completion of treatment, the reduction rate of bilirubin in Yinzhihuang group was higher than that of the other two groups (F = 5.55, P = 0.004). The rate of infants who did not receive phototherapy in Yinzhihuang group was higher than that in phenobarbital group (χ(2) = 47.38, P = 0.000). In Yinzhihuang group, more infants had bowel movements more than five times a day. The incidence of rashes was higher than that in phenobarbital group (P = 0.019), but no significant difference was found as compared with that in phototherapy group (P = 0.339). CONCLUSIONS: About 18% of the term infants who were admitted for jaundice had severe or extremely severe hyperbilirubinemia. Yinzhihuang oral solution combined with phototherapy is effective in bilirubin reduction. Early treatment with Yinzhihuang oral solution may inhibit further increase in bilirubin levels, reduce the phototherapy requirement.

A global need for affordable neonatal jaundice technologies.

Globally, health care providers worldwide recognize that severe neonatal jaundice is a "silent" cause of significant neonatal morbidity and mortality. Untreated neonatal jaundice can lead to death in the neonatal period and to kernicterus, a major cause of neurologic disability (choreo-athetoid cerebral palsy, deafness, language difficulty) in children who survive this largely preventable neonatal tragedy. Appropriate technologies are urgently needed. These include tools to promote and enhance visual assessment of the degree of jaundice, such as simpler transcutaneous bilirubin measurements and readily available serum bilirubin measurements that could be incorporated into routine treatment and follow-up. Widespread screening for glucose-6-phoshate dehydrogenase deficiency is needed because this is often a major cause of neonatal jaundice and kernicterus worldwide. Recognition and treatment of Rh hemolytic disease, another known preventable cause of kernicterus, is critical. In addition, effective phototherapy is crucial if we are to make kernicterus a "never-event." Finally it is essential that we conduct appropriate population-based studies to accurately elucidate the magnitude of the problem. However, knowledge alone is not sufficient. If we are to implement these and other programs and technologies to relegate severe neonatal jaundice and its sequelae to the history books, screening and interventions must be low cost and technologically appropriate for low and middle income nations.

The need to implement effective phototherapy in resource-constrained settings.

Phototherapy is the treatment of choice to reduce the severity of neonatal unconjugated hyperbilirubinemia regardless of its etiology. Its implementation requires a technical framework that conforms to existing evidence-based guidelines that promote its safer and effective use worldwide. Optimal use of phototherapy has been defined by specific ranges of total serum bilirubin thresholds configured to an infant's postnatal age (in hours) and potential risk for bilirubin neurotoxicity. Effective phototherapy implies its use at specific blue light wavelengths (peak emission, 450 ± 20 nm) and emission spectrum (range, 400-520 nm), preferably in a narrow bandwidth that is delivered at an irradiance of ≥30 µW/cm(2)/nm to up to 80% of an infant's body surface area. However, this is often not feasible in clinical settings with limited or constrained resources. To identify and bridge implementation barriers, we propose minimum criteria for device performance for safe and practical use of phototherapy as a prophylactic intervention to prevent severe hyperbilirubinemia.

Effect of induction of meconium evacuation using per rectal laxatives on neonatal hyperbilirubinemia in term infants: a systematic review of randomized controlled trials.

OBJECTIVE: To study the efficacy of early meconium evacuation using per rectal laxatives on the level of serum bilirubin and the need for phototherapy in healthy term infants. MATERIALS AND METHODS: Systematic review of randomized controlled trials comparing per rectal laxatives versus no intervention was conducted using English language articles identified from the Cochrane Central Register of Controlled Trials, Medline, Ovid, and CINAHL databases and bibliographies of selected articles. Eligible studies were assessed for the risk of bias in conduct and reporting. RESULTS: A total of three trials (n = 469) mostly with "unclear risk" were eligible for inclusion. Two trials used glycerin suppository whereas one used glycerin enema for meconium evacuation. Meta-analysis was not possible due to clinical heterogeneity in the choice of laxatives and frequency of intervention. In all the three studies, serum bilirubin levels at 48 h and the need for phototherapy was not significantly different between the two groups. Passage of first meconium and the transitional stools occurred significantly early in the intervention group compared to controls. CONCLUSION: Early evacuation of meconium using per rectal laxatives does not offer any significant clinical advantage for neonatal jaundice.

Metalloporphyrins in the management of neonatal hyperbilirubinemia.

Neonatal jaundice in the first week of life is a common problem in newborns. It is due to an imbalance of bilirubin production and its elimination, which can lead to significantly elevated levels of circulating bilirubin or hyperbilirubinemia. Use of phototherapy and/or exchange transfusion are the current modes for treating neonatal hyperbilirubinemia and preventing any neurologic damage. These strategies, however, only remove bilirubin that has already been formed. Preventing the production of excess bilirubin may be a more logical approach. Synthetic heme analogs, metalloporphyrins, are competitive inhibitors of heme oxygenase, the rate-limiting enzyme in bilirubin production, and their use has been proposed as an attractive alternative strategy for preventing or treating severe hyperbilirubinemia.

Phenobarbitone for prevention and treatment of unconjugated hyperbilirubinemia in preterm neonates: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the role of phenobarbitone in the management of unconjugated hyperbilirubinemia during first two weeks of life in preterm neonates. DESIGN: Meta-analysis. METHODS: A study was eligible for inclusion in the metaanalysis if it randomized preterm neonates into control and treatment groups. Standard search strategy of the Cochrane Neonatal Review Group was used. For categorical and continuous data the odds ratio (OR) and weighted mean difference (WMD) were calculated, respectively. 95% confidence intervals were used and a fixed effects model was assumed for the metaanalysis. MAIN OUTCOME MEASURES: Peak serum bilirubin, duration of phototherapy, need of phototherapy and exchange transfusion, neurodevelopmental outcome and adverse effects. RESULTS: A total of 19 potentially relevant studies were identified. Of these, 3 studies (497 neonates) were included in the metaanalysis. Peak serum bilirubin was significantly lower in phenobarbitone group (mean difference: -1.78 mg/dL, 95% CI: -2.29 to -1.27). Duration of phototherapy was shorter (mean difference: -14.75 h, 95% CI: -26.67 to -2.83). Need of phototherapy (OR: 0.33, 95% CI: 0.13 to 0.81) and exchange transfusion (OR: 0.30, 95% CI: 0.14 to 0.64) were also reduced in phenobarbitone group. CONCLUSION: Phenobarbitone reduces peak serum bilirubin, duration and need of phototherapy and need of exchange transfusion in preterm very low birthweight neonates. Further studies are warranted to evaluate adverse effects and neurodevelopmental outcome.

Pharmacological therapies for unconjugated hyperbilirubinemia.

Severe unconjugated hyperbilirubinemia, seen mainly in neonates, may cause kernicterus and death. Conventional treatment for severe unconjugated hyperbilirubinemia consists of phototherapy and exchange transfusion. Phototherapy, however, has several known disadvantages while exchange transfusion is associated with a significant morbidity, and even mortality. These harmful effects indicate the need to develop alternative pharmacological treatment strategies for unconjugated hyperbilirubinemia. Generally, these strategies aim to decrease the plasma concentration of unconjugated bilirubin (UCB) by inhibiting production, stimulating hepatic clearance, or interrupting the enterohepatic circulation of the pigment. To be considered for routine clinical use, an alternative treatment strategy should be less invasive and at least as effective and safe as phototherapy. Several pharmacological therapies such as metalloporhyrins, clofibrate, bile salts, laxatives and bilirubin oxidase may meet these criteria in the future, but none of them has yet been evaluated sufficiently to allow routine application. This review aims to discuss the state of the art and future perspectives in pharmacological treatment of neonatal jaundice.

[Colonic dripping with Taihuang liquid for treatment of neonatal hyperbilirubinemia].

OBJECTIVE: To explore the clinical effects of colonic dripping with Taihuang liquid (THL) in treating neonatal hyperbilirubinemia (HBE). METHODS: One hundred and thirty-eight neonates with HBE were randomly assigned to two groups. Conventional treatment and nursing were given to both groups, and THL was given additionally to the observation group by colonic dripping. RESULTS: Significant differences between the observation group and the control group were shown in frequency of defecation (4.6 +/- 1.3 times/d vs 2.0 +/- 1.1 times/d), daily serum bilirubin reduction (31.5 +/- 10.1 micromol/L vs 23.3 +/- 8.3 micromol/L), and days for normalizing serum bilirubin level (5.6 +/- 3.5 d vs 7.8 +/- 4.1 d, all P < 0.01). CONCLUSION: Colonic dripping of THL could promote the excretion of bilirubin, so as to decrease the level of serum bilirubin in neonates with HBE.