Effect of Oral Zinc Supplementation on Serum Bilirubin Levels in Term Neonates With Hyperbilirubinemia Undergoing Phototherapy: A Double-blind Randomized Controlled Trial.

BACKGROUND: Background: Enterohepatic bilirubin circulation is one of the determinants of neonatal jaundice. OBJECTIVE: To evaluate the role of oral zinc in reducing serum bilirubin in term neonates with hyperbilirubinemia. STUDY DESIGN: Double-blind, randomized, placebo-controlled trial. PARTICIPANTS: 106 term neonates with jaundice within the phototherapy range admitted to a level III neonatal intensive care unit. INTERVENTION: Neonates were randomized and allocated to receive either oral zinc sulfate (5 mg/day) or matching placebo for 5 days. Both groups received conventional phototherapy as per American Academy of Pediatrics (AAP) guidelines. OUTCOMES: Primary: Reduction in total serum bilirubin levels at 24, 48, 72, and 96 hr after intervention. Secondary: Duration of phototherapy, and hospital stay. RESULTS: The mean (SD) total serum bilirubin levels in zinc and placebo groups were 15.3 (2.85) vs 17.1 (2.21) mg/dL (MD 1.74; P<0.001) at 24 h; 11.7 (4.46) vs. 14.62 (3.83) mg/dL (MD 2.89; P<0.001) at 48 h; 6.7 (4.77) vs 9.5 (3.70) mg/dL (MD 2.79; P <0.001) at 72 h; and 5.1 (3.95) vs 6.5 (3.70) mg/dL (MD 1,49; P=0.045) after 72 hr, respectively. The mean (SD) duration of phototherapy was significantly lower in zinc group than placebo group [ 53.42 (19.62) vs 71.4 (19.43) h; P<0.001]. There was no significant difference in hospital stay between the two groups [mean (SD) 81.05 (19.43) vs 86.25 (20.02) h; P= 0.227]. CONCLUSION: Oral zinc sulfate supplementation at a dose of 5 mg once a day along with phototherapy significantly reduced total and indirect serum bilirubin levels and also reduced the total duration of phototherapy required in the term neonatal hyperbilirubinemia, with minimal or no adverse effects.

Intrapartum Maternal Prophylactic Antimicrobial Treatment and Neonatal Jaundice.

Intrapartum antibiotics are widely used and may potentially affect bilirubin levels and neurotoxicity in the newborn. The aim of this study was to examine the effect of intrapartum antibiotic exposure on neonatal jaundice. We retrospectively collected data from 972 neonates born to 963 mothers. Five hundred forty-five mothers (56.6%) received intrapartum antibiotics. There were no statistically significant differences in maximum bilirubin level (7.82 ± 3.65 vs 7.63 ± 3.71, P = .43) or need for phototherapy (9 [1.62%] vs 4 [0.94%], P = .52) between exposed and non-exposed newborns. The rate of phototherapy was significantly higher only in the group of infants born to mothers who received broad-spectrum antibiotics at 2 to 3.9 hours prior to delivery (χ2 = 10.453, P = .015) and was not higher in the group of exposure >4 hours, which may represent a short transient effect of antibiotics exposure on bilirubin turnover. Further studies are needed to validate this finding.

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.

Therapeutic efficacy and safety of Yinzhihuang granules with phototherapy in neonatal pathologic jaundice: An updated systematic review and meta-analysis.

BACKGROUND: Yinzhihuang granule, consisting of extracts of Artemisia capillaris Thunb., Gardenia jasminoides Ellis, Lonicera japonica Thunb., and Scutellaria baicalensis Georgi is a well-known traditional Chinese patent medicine for patients with liver injury in China. However, the effects and safety of its use for pathologic jaundice in newborns require further systematic evaluation. PURPOSE: To systematically evaluate the efficacy and safety of Yinzhihuang granules for the treatment of neonatal pathologic jaundice and to provide clinical evidence. METHODS: Chinese databases (China Network Knowledge Infrastructure, Wan Fang Database, and VIP Database) and English databases (PubMed, EmBase, and the Cochrane Library) were thoroughly investigated through screening randomized controlled trials on Yinzhihuang granules for neonatal pathologic jaundice from the establishment of all databases to November 18, 2021. A meta-analysis was performed for selected data using STATA software. TSA software was used for trial sequential analyses of the total effective rate and adverse reactions. RESULTS: A total of 19 trials and 2,221 newborns with pathologic jaundice were included in this study. Outcome measures of clinical efficacy in the experimental group were higher than in controls, including total bilirubin (WMD = -30.34, 95% CI = -35.44 to -25.23, p < 0.001), direct bilirubin (WMD = -15.03, 95% CI = -23.54 to -6.52, p < 0.001), indirect bilirubin (WMD = -11.22, 95% CI = -17.50 to -4.95, p < 0.001), recovery time (WMD = -2.96, 95% CI = -3.92 to -2.00, p < 0.001), hospitalization time (WMD = -3.83, 95% CI = -4.89 to -2.76, p < 0.001), and liver function indices. There were statistically significant differences between the two groups. Likewise, the incidence of adverse reactions, including diarrhea, erythra, and fever decreased remarkably in the trial group (RR = 0.44, 95% CI =  0.33 to 0.59, p < 0.001). Publication bias did not exist. We verified the efficacy and safety of Yinzhihuang granules with phototherapy for pathologic jaundice in newborns according using TSA analysis. CONCLUSION: Yinzhihuang granules with phototherapy for neonatal pathologic jaundice are more effective than phototherapy alone. The incidence of ADRs does not increase with the application of Yinzhihuang granules. Due to the heterogeneity across the included studies, additional multicenter clinical trials with follow-ups are needed to confirm our findings.

Gut microbial alterations in neonatal jaundice pre- and post-treatment.

Neonatal jaundice is a common disease that affects up to 60% of newborns. Herein, we performed a comparative analysis of the gut microbiome in neonatal jaundice and non-neonatal jaundice infants (NJIs) and identified gut microbial alterations in neonatal jaundice pre- and post-treatment. We prospectively collected 232 fecal samples from 51 infants at five time points (0, 1, 3, 6, and 12 months). Finally, 114 samples from 6 NJIs and 19 non-NJI completed MiSeq sequencing and analysis. We characterized the gut microbiome and identified microbial differences and gene functions. Meconium microbial diversity from NJI was decreased compared with that from non-NJI. The genus Gemella was decreased in NJI versus non-NJI. Eleven predicted microbial functions, including fructose 1,6-bisphosphatase III and pyruvate carboxylase subunit B, decreased, while three functions, including acetyl-CoA acyltransferase, increased in NJI. After treatments, the microbial community presented significant alteration-based ß diversity. The phyla Firmicutes and Actinobacteria were increased, while Proteobacteria and Fusobacteria were decreased. Microbial alterations were also analyzed between 6 recovered NJI and 19 non-NJI. The gut microbiota was unique in the meconium microbiome from NJI, implying that early gut microbiome intervention could be promising for the management of neonatal jaundice. Alterations of gut microbiota from NJI can be of great value to bolster evidence-based prevention against 'bacterial dysbiosis'.

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.

Evaluating the effects of different doses of ursodeoxycholic acid on neonatal jaundice.

BACKGROUND: Icterus tends to be one of the most prevalent causes of neonatal hospitalization. The present study aimed to evaluate the effects of the different doses of ursodeoxycholic acid (UDCA) on neonatal jaundice. METHOD: In this study, 120 newborns who were hospitalized for phototherapy were randomly assigned. Group A received phototherapy and UDCA 5 mg/kg/dose every 12 hours orally, group B patients were treated with phototherapy and UDCA 7.5 mg/kg/dose every 12 hours orally. Group C received phototherapy with a placebo. All patients were evaluated for bilirubin levels, the duration of phototherapy, and the length of hospital stay. RESULTS: The mean bilirubin level at hospital admission was 19.88 ± 2.33 mg/dl in group A, 19.33 ± 2.51 mg/ dl in group B, and 19.76 ± 2.64 mg/dl in group C (p= 0.58). The groups receiving phototherapy with UDCA showed a significant decrease in the bilirubin level. Bilirubin level decreased to 10.04 ± 1.11mg/dl in group A, 8.82 ± 1.11 mg/dl in group B, and 12.04 ± 2.05 mg/dl in group C (p= 0.000). Furthermore, the mean duration of phototherapy, as well as the average length of hospital stay, were significantly lower in group B as compared to the other groups (p= 0.000). CONCLUSION: The findings of this study indicated that the administration of UDCA in addition to phototherapy could effectively decrease the length of hospital stay and bilirubin levels in neonatal hyperbilirubinemia. However, further studies with a larger sample size are required before one can recommend the routine use of UDCA for the treatment of neonatal jaundice.

[Systematic review and Meta-analysis of effect of Yinzhihuang Oral Liquid in treatment of neonatal jaundice].

To systematically review effectiveness and safety of Yinzhihuang Oral Liquid in the treatment of neonatal jaundice. A systematic retrieval was performed throughout China National Knowledge Infrastructure( CNKI),Wan Fang,VIP,Sino Med and PubMed,Medline,Cochrane Library databases from the establishment to April 2019. Randomized controlled trials of Yinzhihuang Oral Liquid in treatment of neonatal hyperbilirubinemia were retrieved. Clinical studies in line with the inclusion criteria were involved for data extraction,and the quality of the included literatures was evaluated by the risk bias assessment tool in the Cochrane review manual. Finally,Meta-analysis was performed by Rev Man 5.3 software. A total of 30 studies were involved,involving 3 923 child patients,including1 940 in observation group and 1 983 in control group. According to the results of Meta-analysis,the total effective rate( RR = 1. 22,95%CI[1. 18,1. 26],P<0. 000 01),level of TBi L after treatment( MD =-38. 78,95%CI[-48. 38,-29. 18],P<0. 000 01),time to jaundice resolution( MD =-1. 76,95% CI[-2. 10,-1. 41],P < 0. 000 01) and daily average decrease value of bilirubin( MD =11. 67,95%CI[8. 89,14. 45],P<0. 000 01) of observation group were significantly better than those of control group,with statistically significant differences. Adverse reactions were reported in nine studies,mainly including diarrhea,vomiting,fever,rash and other symptoms,which did not affect the treatment effect. The effectiveness of Yinzhihuang Oral Liquid combined with conventional therapy in treating neonatal jaundice was better than conventional therapy alone,with little adverse reactions. However,most of literatures included had a low research quality,which impacted the reliability of the conclusion. Therefore,it is suggested to conduct more largesample-size,multicenter,scientifically designed,strictly implemented high-quality randomized controlled trials in the future,in order to study the efficacy and safety of Yinzhihuang Oral Liquid in the treatment of neonatal jaundice.

Ursodeoxycholic acid versus phenobarbital for cholestasis in the Neonatal Intensive Care Unit.

BACKGROUND: Although neonates and young infants with cholestasis are commonly treated with either phenobarbital or ursodeoxycholic acid (ursodiol), there is no evidence that phenobarbital is effective for this indication. Our objective was to compare the effectiveness of ursodiol and phenobarbital for the treatment of cholestasis in a diverse NICU population. METHODS: This is a retrospective cohort study including infants with cholestasis who were admitted to a Level IV NICU between January 2010 and December 2015. Drug courses of phenobarbital and ursodiol were identified within the medical record, and medical, demographic, and drug information were extracted. The primary outcome was reduction in direct bilirubin. RESULTS: Sixty-eight infants provided a total of 112 courses of drug therapy for comparison. Diverse medical diagnoses were captured in the patient cohort. Ursodiol was significantly more effective in reducing direct bilirubin than was phenobarbital (- 1.89 vs + 0.76 mg/dL; - 33.33 vs + 13.0 umol/L, p-value 0.03), even after controlling for baseline cholestasis severity, intrauterine growth restriction status, and lipid lowering therapy (- 2.16 vs + 0.27 mg/dl; - 36.94 vs + 4.62 umol/L, p-value 0.03). There was no improvement in direct bilirubin in the majority of infants treated with phenobarbital. CONCLUSIONS: Phenobarbital, as compared to ursodiol, has limited efficacy for the reduction of direct bilirubin in neonates and young infants with cholestasis. Given new data regarding the potential neurotoxicity of phenobarbital in the developing brain, providers may choose to avoid phenobarbital in the treatment of cholestasis in infants.

The influence of zinc sulfate on neonatal jaundice: a systematic review and meta-analysis.

INTRODUCTION: Zinc sulfate may be a promising approach to treat neonatal jaundice. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc sulfate on hyperbilirubinemia among neonates. METHODS: PubMed, EMbase, Web of science, EBSCO, Cochrane library databases, Ovid, BMJ database, and CINAHL were systematically searched. Randomized controlled trials (RCTs) assessing the effect of zinc sulfate versus placebo on the prevention of jaundice in neonates were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcomes were total serum bilirubin (TSB) on three days and seven days, the incidence of hyperbilirubinemia. Meta-analysis was performed using random- or fixed-effect models. RESULTS: Five RCTs involving 645 patients were included in the meta-analysis. Overall, compared with placebo, zinc sulfate supplementation failed to significantly reduce TSB on three days (mean difference (MD) = 0.09 mg/dL; 95% confidence interval (CI) = -0.49 to 0.67; p = .77), TSB on seven days (MD = -0.37 mg/dL; 95% CI = -98 to 0.25; p = .25) as well as the incidence of hyperbilirubinemia (OR = 1.14; 95% CI = 0.74 to 1.76; p = .56). Zinc sulfate showed no influence on phototherapy requirement (OR = 0.90; 95% CI = 0.41 to 1.98; p = .79), but resulted in significantly decreased duration of phototherapy (MD = -16.69 h; 95% CI = -25.09 to -8.3 h; p < .0001). CONCLUSIONS: Zinc sulfate could not reduce the TSB on three days and seven days, the incidence of hyperbilirubinemia and phototherapy requirement, but lead to significantly decreased duration of phototherapy.

Primary health workers' knowledge and practices relating to neonatal jaundice in Ibadan, Nigeria.

BACKGROUND: Over half of births and newborn care occur in primary healthcare facilities in Nigeria, but information on activities of personnel working there is scarce. AIM: To assess the knowledge and practices relating to neonatal jaundice (NNJ) among community health workers (CHWs) and community birth attendants (CBAs) in Nigeria. SETTING: We conducted a cross-sectional survey of all 227 CHWs and 193 registered CBAs in Ibadan, Nigeria. METHODS: Knowledge and practices regarding NNJ were measured using a pretested questionnaire. Knowledge and practices were assessed on a 33-point scale and a 13-point scale, respectively. Scores ≤  17 and ≤  9 was regarded as poor knowledge and as wrong practice, respectively. RESULTS: Many (64.5%) of the respondents could not correctly describe examination for NNJ (CHWs: 49.4%; CBAs: 50.6%). Of the 200 (47.6%) who treated NNJ 3 months prior to the study, 62.5% (CHWs: 66.9% and CBAs: 53.7%) treated NNJ with orthodox drugs. Drugs prescribed included: antibiotics (93.3%), antimalarials (5.3%), multivitamins (28.0%), paracetamol (6.2%) and phenobarbitone (7.1%). Significantly more CHWs than CBAs practiced exposure to sunlight (33.1% versus 16.4%) and administration of glucose water (28.6% versus 14.9%), while 58.0% of all respondents referred cases to secondary health facilities. Overall, 80.2% had poor knowledge (CHWs: 78.9%; CBAs: 81.9%) and 46.4% engaged in wrong practices (CHWs: 57.3%; CBAs: 33.7%). CHWs were more likely to indulge in wrong practices than CBAs (OR = 2.22, 95% CI = 1.03, 4.79). CONCLUSION: Primary Health Workers in Ibadan had poor knowledge and engaged in wrong practices about NNJ. The needs to organise regular training programmes were emphasised.

Ethnomedicine for neonatal jaundice: A cross-sectional survey in Qom, Iran.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Medicine (TM) is popularly used for neonatal jaundice in Iran. OBJECTIVE: to provides evidence for characteristics of traditional medicine use in the treatment of neonatal jaundice in Qom, Iran. MATERIALS AND METHODS: Field surveys were carried out during July 2015 - August 2015 in Qom through structured questionnaire in Persian from 212 parents of children with neonatal jaundice. All plant species recorded for the treatment of neonatal jaundice were sampled. Samples were identified by a botanist and obtained a voucher specimens number and deposited in the Shiraz School of Pharmacy Herbarium. The information such as scientific name, family, local name, parts used and preparation method were provided. The Use Value (UV), Frequency of Citation (FC), Relative Frequency of Citation (RFC) and Relative Family Importance Value (FIV) are also calculated. RESULTS: In total, 165 (78%) of participants reported the use of traditional methods for their neonates. The use of herbal remedies was the most popular form of these traditional interventions. A total of 8 plant species belonging to 7 families were identified. Cotoneaster nummularioides Pojark. Cichorium intybus L. Alhagi maurorum Medik. Descurainia sophia (L.) Webb ex Prantl were most frequent herbs used by neonates and their feeding mother to treat jaundice. Manna was the most popular plant part and distillation and soaking were most frequent preparation methods in these patients. The use of TM in these patients is associated with their previous experience on TM use and their view on its potential risk. CONCLUSIONS: This study provided information on the prevalence, associated factors and characteristics of traditional medicine use along with ethnomedicinal knowledge from Qom in Iran on neonatal jaundice.

Use of intravenous immunoglobulin in neonates at a tertiary academic hospital: a retrospective 11-year study.

BACKGROUND: Intravenous immunoglobulin (IVIG) is used to treat a variety of diseases in the neonatal intensive care unit (NICU). Although audits have reported on the spectrum of IVIG use in adults, the indications and utilization in neonates has not been investigated. The objectives of this study were to describe the usage pattern of and indications for IVIG in a tertiary care NICU. STUDY DESIGN AND METHODS: A retrospective chart review was performed of all neonates who received IVIG in the NICU from January 2003 to December 2013. Data collected included patient demographic features, antenatal maternal details, neonatal laboratory results, treatment details, adverse events, and patient outcome. RESULTS: Thirty-seven neonates received IVIG over the 11-year period. Twenty-three (67%) were treated for hemolytic disease of the newborn (HDN); 13 treatments were ABO related, six were anti-D related, and four were for clinically significant antibodies. Fourteen (33%) were treated for non-HDN causes, including eight for septic neonates, two for neonates with necrotizing enterocolitis, two for neonates with a clinically significant antibody but without evidence of hemolysis, and two for neonates with glucose 6-phosphate dehydrogenase deficiency. A complete hemolytic workup was not performed consistently before the receipt of IVIG. CONCLUSIONS: This novel assessment of IVIG use in the NICU revealed the spectrum of disease for which IVIG is ordered. This study also found that key diagnostic tests needed to confirm an immune etiology for idiopathic jaundice are not performed routinely before IVIG receipt. Neonatal transfusion-related databases are needed to carry out pragmatic clinical trials to establish better evidence-based guidelines for IVIG therapy in the NICU.

Therapeutic effect of Agaricus brasiliensis on phenylhydrazine-induced neonatal jaundice in rats.

The present study was designed to investigate the effect of Agaricus brasiliensis extract (ABE) on phenylhydrazine-induced neonatal jaundice in rats. Administration of ABE dose-dependently reduced the elevated bilirubin level induced by phenylhydrazine. It can be somewhat supported from the results of in vitro bilirubin degradation experiment. ABE treatment also reduced the total antioxidant status (TAOS), cascade O2(-)/SOD, level of NF-κB protein, and adrenomedullin (AM). Overall, the results of this study demonstrated that Agaricus brasiliensis extract may be beneficial to reducing bilirubin level without causing hepatotoxicity in neonatal jaundice.

Perforated appendicitis after intravenous immunoglobulin therapy in a term neonate with haemolytic jaundice.

Neonatal appendicitis is a rare clinical condition that may cause high morbidity and mortality if diagnosis is delayed. There is usually an underlying disease; it can also be a localized form of necrotizing enterocolitis. Here, we present a term neonate who was treated with intravenous immunoglobulin because of severe isoimmune hemolytic jaundice. The patient developed abdominal symptoms within 10 hours of therapy, was diagnosed with acute perforated appendicitis and completely recovered after surgery.

Pattern and predictors of maternal care-seeking practices for severe neonatal jaundice in Nigeria: a multi-centre survey.

BACKGROUND: Nigeria is frequently associated with disproportionately high rates of severe neonatal jaundice (NNJ) underpinned by widespread Glucose-6-phosphate dehydrogenase (G6PD) deficiency. Timely and appropriate treatment of NNJ is crucial for preventing the associated morbidity and neuro-developmental sequelae. Since mothers are likely to be the first mostly to observe the onset of severe illness in their newborns, we set out to identify the pattern and predictors of maternal care-seeking practices for NNJ in three culturally-distinct settings in Nigeria. METHODS: A multi-centre study was conducted among women attending antenatal clinics in Abuja, Lagos and Port Harcourt from October 2011 to April 2012 using a pretested questionnaire. Predictors of awareness of NNJ, accurate recognition of NNJ, use of potentially harmful therapies and preference for future hospital treatment were determined with multivariate logistic regressions. RESULTS: Of the 488 participants drawn from the three locations, 431 (88.3%) reported awareness of NNJ, predominantly (57.8%) attributable to professional health workers. A total of 309 (63.3%) mothers with prior knowledge of NNJ claimed they could recognise NNJ, but 270 (87.4%) from this group accurately identified the features of NNJ. Multiparous mothers (Adjusted odds ratio, AOR:4.05; 95% CI:1.75-9.36), those with tertiary education (AOR:1.91; CI:1.01-3.61), and those residing in Lagos (AOR:2.96; CI:1.10-7.97) were more likely to have had prior knowledge of NNJ. Similarly, multiparous mothers (AOR:2.38; CI:1.27-4.46) and those with tertiary education (AOR:1.92; CI:1.21-3.05) were more likely to recognise an infant with jaundice accurately. Mothers educated by health workers were 40% less likely to resort to potentially harmful treatment for NNJ (AOR:0.60; CI:0.39-0.92) but more likely to seek hospital treatment in future for an infant suspected with jaundice (AOR:1.88; CI:1.20-2.95). CONCLUSIONS: Women with tertiary education and multiparous mothers who attend routine antenatal clinics are more likely than less educated women, to be associated with appropriate care-seeking practices for infants with NNJ regardless of the socio-cultural setting. Systematic efforts by professional health workers are warranted, as part of routine antenatal care, to engage other groups of mothers especially those likely to indulge in self-use of potentially harmful therapies.

Impact of fatty acids on human UDP-glucuronosyltransferase 1A1 activity and its expression in neonatal hyperbilirubinemia.

While breast milk has been known as a cause of neonatal hyperbilirubinemia, the underlying mechanism of breast milk-induced jaundice has not been clarified. Here, the impact of fatty acids on human UDP-glucuronosyltransferase (UGT) 1A1--the sole enzyme that can metabolize bilirubin--were examined. Oleic acid, linoleic acid, and docosahexaenoic acid (DHA) strongly inhibited UGT1A1 activity. Forty-eight hours after a treatment with a lower concentration of DHA (10 mg/kg), total bilirubin significantly increased in neonatal hUGT1 mice, which are human neonatal jaundice models. In contrast, treatments with higher concentrations of fatty acids (0.1-10 g/kg) resulted in a decrease in serum bilirubin in hUGT1 mice. It was further demonstrated that the treatment with higher concentrations of fatty acids induced UGT1A1, possibly by activation of peroxisome proliferator-activated receptors. Our data indicates that activation of peroxisome proliferator-activated receptors would increase UGT1A1 expression, resulting in reduction of serum bilirubin levels in human infants.

Bilirubin clearance and antioxidant activities of ethanol extract of Phyllanthus amarus root in phenylhydrazine-induced neonatal jaundice in mice.

The ability of ethanol extract of Phyllanthus amarus root (EEPA) to decrease bilirubin level and oxidative stress in phenylhydrazine-induced neonatal jaundice in mice was investigated. Administration of phenylhydrazine (75 mg/kg b.w.) significantly elevated total and unconjugated serum bilirubin level compared to control mice. EEPA (5, 10, and 20 mg/kg b.w., oral) dose-dependently reduced the bilirubin level. EEPA treatment also upregulated hepatic CAR and CYP3A1, accounting for its ability to facilitate bilirubin clearance. A single dose of EEPA (20 mg/kg b.w.) induced higher level of bilirubin clearance than phototherapy, widely used for treating neonatal jaundice. Furthermore, phenylhydrazine administration significantly increased MDA, protein carbonyl, and total thiol content and lowered the GSH level along with superoxide dismutase and catalase activity in erythrocyte compared to the control group. Single administration of EEPA (20 mg/kg b.w.) significantly reversed the trend. Presence of gallic acid, gentisic acid, and ortho-coumaric acid in EEPA was identified by HPLC analysis. Amongst these, the major phenolic constituent, gallic acid, exhibited significant bilirubin-lowering effect. These results suggested that P. amarus may be beneficial in reducing bilirubin level as well as oxidative stress in neonatal jaundice.

Lipid peroxidation is not the primary mechanism of bilirubin-induced neurologic dysfunction in jaundiced Gunn rat pups.

BACKGROUND: Hazardous levels of bilirubin produce oxidative stress in vitro and may play a role in the genesis of bilirubin-induced neurologic dysfunction (BIND). We hypothesized that the antioxidants taurourosdeoxycholic acid (TUDCA), 12S-hydroxy-1,12-pyrazolinominocycline (PMIN), and minocycline (MNC) inhibit oxidative stress and block BIND in hyperbilirubinemic j/j Gunn rat pups that were given sulfadimethoxine to induce bilirubin encephalopathy. METHODS: At peak postnatal hyperbilirubinemia, j/j Gunn rat pups were dosed with sulfadimethoxine to induce bilirubin encephalopathy. Pups were given TUDCA, PMIN, MNC, or vehicle pretreatment (15 min before sulfadimethoxine). After 24 h, BIND was scored by using a rating scale of neurobehavior and cerebellar tissue 4-hydroxynonenal and protein carbonyl dinitrophenyl content were determined. Nonjaundiced heterozygous N/j pups served as controls. RESULTS: Administration of sulfadimethoxine induced BIND and lipid peroxidation but not protein oxidation in hyperbilirubinemic j/j pups. TUDCA, PMIN, and MNC each reduced lipid peroxidation to basal levels observed in nonjaundiced N/j controls, but only MNC prevented BIND. CONCLUSION: These findings show that lipid peroxidation inhibition alone is not sufficient to prevent BIND. We speculate that the neuroprotective efficacy of MNC against BIND involves action(s) independent of, or in addition to, its antioxidant effects.

Single dose of 50 mg/kg clofibrate in jaundice of healthy term neonates: randomised clinical trial of efficacy and safety.

OBJECTIVE: To evaluate the effect of single oral dose of 50 mg/kg clofibrate in hyperbilirubinemia of term healthy neonates in Yazd, Iran. METHODS: A parallel single- blinded randomized clinical trial, conducted on 60 healthy term neonates admitted between July and December 2007 to Shahid Sadoughi Hospital. Inclusion criteria were neonates with gestation age of 38-42 wk, birth weight of 2500-4000 g, product of normal vaginal delivery, breast-fed and total serum bilirubin (TSB) level of 17-29.9 mg/dL. Neonates with sepsis, anemia, severe asphyxia, hemolytic diseases, major congenital anomalies, indirect hyperbilirubinemia and underlying hepatic disorders were excluded. Selection of patients was based on random allocation via table of random numbers and the patients distributed into two groups. In group one, 30 neonates were treated with phototherapy alone and in 30 of other group treatment done with single dose of 50 mg/kg clofibrate and phototherapy. The primary endpoint with respect to efficacy in reducing of TSB was achieving TSB to less than 14 mg/dL as measured at the beginning, 12, 24 and 48 h after the start of phototherapy. Secondary outcomes were hospital stay days, duration of phototherapy and side effects of treatments during hospital stay and on the second day after discharge. RESULTS: No significant differences were seen from the viewpoint of rout of delivery, gender, gestational age, birth weight, hemoglobin and bilirubin level at time of admission and weight in discharge time in the two groups. After 48 h of intervention, 27 (90%) neonates in clofibrate group and 15 (56.7%) in control group had TSB of less than 14 mg/dL (p 0.02). Mean TSB 12 h after treatment (mean ± SD: 14.82 ± 1.7 mg/dL vs. 16.67 ± 1.77 mg/dL, P 0.001), 24 h after treatment (mean ± SD: 11.97 ± 2.92 mg/dL vs. 14.61 ± 2.52 mg/dL, P 0.001) and 48 h after treatment (mean ± SD: 7.91 ± 2.45 mg/dL vs. 12.74 ± 2.21 mg/dL, P 0.0001), mean of hospital stay days (mean ± SD: 1.7 ± 0.7 days vs. 3.2 ± 1.2 days, P 0.03) and duration of phototherapy (mean ± SD: 30.2 ± 13.99 h vs. 46.2 ± 15.58 h, P 0.001] were significantly lower in clofibrate group. Only loose stool was seen in two patients of clofibrate group and no significant difference was seen from view of safety of the treatments. CONCLUSIONS: A single dose of 50 mg/kg clofibrate in treatment of neonatal hyperbilirubinemia is effective, safe and cost effective in view of reducing hospital stay days.