Hyperbilirubinemic Infants Research Articles

Comparison of prognosis between hyperbilirubinemic infants with and without hypernatremia.

Hypernatremia may facilitate the diffusion of bilirubin through the blood-brain barrier and increase the risk of bilirubin encephalopathy. This study was conducted to compare the prognosis of jaundice infants with those with jaundice and hypernatremia. A total of 615 term infants with idiopathic jaundice with or without hypernatremia were enrolled in this cohort study with 24-months follow-up at Ghaem Hospital, Mashhad, Iran, between 2010 and 2022. An in-house questionnaire including the laboratory evaluation and neonatal characteristics was used as the data collection tool. The follow-up of neonatal development status was performed using the Denver test II at 6, 12, 18, and 24 months after discharging from hospital. Normal outcomes were seen in 555 (90.2%) out of 615 studied infants, while 60 cases (9.8%) showed abnormal outcomes. Serum levels of sodium (P = 0.017), bilirubin (P = 0.001), urea (P = 0.024), and creatinine (P = 0.011) as well as hyperthermia (P = 0.046) and unconsciousness (P = 0.005) showed significant differences between the two groups. Approximately 16% of the newborns with both jaundice and hypernatremia, and 9% of those with only jaundice had unfavorable prognoses. Also, bilirubin level had the most predictive power (91.3%). Our results suggest that hypernatremia or jaundice alone, may affect the prognosis of infants aged 2 years; but jaundice and hypernatremia together, will intensify the developmental problems in jaundice infants. However, the role of hyperbilirubinemia in the incidence of complications is more than hypernatremia.

THE RELATIONSHIP BETWEEN EFFECTIVENESS OF BREASTFEEDING WITH THE INCIDENCE OF PHYSIOLOGIC HYPERBILIRUBINEMIA IN NEONATAL MATURE AGE OF 2-4 DAYS

Newborn who receive initation of breastfeeding effectively and colostrum is believed to reduce incidence of physiologic hyperbilirubinemia. breastfeeding.The purpose of this study was to the effectiveness of breastfeeding relationship with the incidence of physiologic hyperbilirubinemia in infants mature age of 2-4 days.This study uses a descriptive quantitative analytic method with a cross-sectional approach. Data were taken from the baby room of RSIA UMMI Bogor in November 2015. Respondents from this study were all mothers of infants and hyperbilirubinemic infants who met the inclusion criteria. The sampling technique was total sampling, namely all members of the population were used as a sample of 30 respondents. Data collection using a questionnaire. The data analysis used univariate analysis which was presented in the frequency distribution table while the bivariate data used the chi-square test. From the results of the study, it was found that the effectiveness of breastfeeding with the incidence of hyperbilirubinemia where out of 12 (40%) mothers who were ineffective in breastfeeding their babies experienced hyperbilirubinemia. And based on the chi-square test, there was a relationship between the effectiveness of breastfeeding and the incidence of hyperbilirubinemia (p = 0.027). The effectiveness of breastfeeding can reduce the incidence of hyperbilirubin in infants. The faster and more often the mother gives breast milk to her baby, the faster and more milk production will be to meet nutritional intake The important role of health workers in the success of breastfeeding or breastfeeding, should add knowledge about lactation, so that it can help post partum mothers if there are problems with breastfeeding. There is also a need for a professional breastfeeding counselor in dealing with breastfeeding problems.

Cord blood bilirubin and prediction of neonatal hyperbilirubinemia and perinatal infection in newborns at risk of hemolysis

ObjectiveTo assess the accuracy of umbilical cord bilirubin values to predict jaundice in the first 48h of life and neonatal infection. MethodNewborn infants treated at a regional well-baby nursery born at ≥36 weeks of gestation were included in this retrospective cohort study. All infants born in a 3-year period from mothers with O blood type and/or Rh-negative were included and had the umbilical cord bilirubin levels measured. Hyperbilirubinemia in the first 48h was defined as bilirubin levels above the phototherapy threshold. Neonatal infection was defined as any antibiotic treatment before discharge. ResultsA total of 1360 newborn infants were included. Two hundred and three (14.9%) newborn infants developed hyperbilirubinemia in the first 48h of life. Hyperbilirubinemic infants had smaller birth weight, higher levels of umbilical cord bilirubin, a higher rate of infection and were more often direct antiglobulin test positive. Umbilical cord bilirubin had a sensitivity of 76.85% and a specificity of 69.58% in detecting hyperbilirubinemia in the first 48h, with the cut-off value at 34μmol/L. The area under the receiver operating characteristic curve was 0.80 (95% CI: 0.78–0.82). Umbilical cord bilirubin had a sensitivity of 27.03% and specificity of 91.31% in detecting perinatal infection. The area under the receiver operating characteristic (ROC) curve was 0.59 (95% CI: 0.57–0.63). ConclusionsA positive correlation was found between umbilical cord bilirubin and hyperbilirubinemia in the first 48h of life. Umbilical cord bilirubin is a poor marker for predicting neonatal infection.

Noninvasive Detection of Hemolysis with ETCOc Measurement in Neonates at Risk for Significant Hyperbilirubinemia

Background: Hemolytic hyperbilirubinemia due to blood group incompatibility or glucose-6-phosphate dehydrogenase deficiency (G6PD) is a common cause of significant hyperbilirubinemia. Hemolysis in a hyperbilirubinemic infant increases the risk of bilirubin neurotoxicity. A new portable device (CoSense) can rapidly detect breath end-tidal carbon monoxide corrected to ambient carbon monoxide (ETCOc). ETCOc levels are surrogate markers of hemoglobin breakdown and bilirubin production. Objective: The aim was to evaluate the association between ETCOc values and hemolysis and its relevance in neonates at risk for significant hyperbilirubinemia. Methods: A prospective study was conducted among newborn infants born at more than 35 weeks and with a birth weight greater than 2,000 g with a G6PD deficiency, blood group incompatibility, or clinical jaundice needing phototherapy during the first 7 days of life. The recruited infants had their breath ETCOc measured twice, first on the day of recruitment and then again on the following day. Results: Fifty infants completed this study. Their mean ETCOc was 1.61 (±0.56) ppm. There was a linear correlation (r = 0.89) between increasing ETCOc values and reticulocyte counts (RC). Sixteen newborns with ABO incompatibility had a significantly higher mean ETCOc of 1.98 ppm (±0.71) as compared to 1.43 (±0.38) ppm in the nonhemolytic hyperbilirubinemia (NHH) group (n = 25) (p = 0.002). This was suggestive of hemolysis as shown by the significantly higher RC of 6.90% (±3.38) compared to 4.68 (±1.26) in the NHH group (p <0.005). Neonates with an ETCOc level ≥1.8 ppm had a higher RC, a lower hemoglobin level, higher serum bilirubin levels, and a rapid rise in serum bilirubin and needed a longer duration of phototherapy. ETCOc values ≥1.8 ppm were suggestive of hemolysis (RC ≥6%), with a sensitivity of 90% and a specificity of 83%. Conclusion: Higher ETCOc values ≥1.8 ppm are suggestive of hemolysis and they are associated with significant hyperbilirubinemia.

Hyperbilirubinemia in preterm infants in Japan: New treatment criteria.

In 1992, Kobe University proposed treatment criteria for hyperbilirubinemia in newborns using total serum bilirubin and serum unbound bilirubin reference values. In the last decade, chronic bilirubin encephalopathy has been found to develop in preterm infants in Japan because it can now be clinically diagnosed based on an abnormal signal of the globus pallidus on T2-weighted magnetic resonance imaging and abnormal auditory brainstem response with or without apparent hearing loss, along with physical findings of kinetic disorders with athetosis. We therefore revised the Kobe University treatment criteria for preterm hyperbilirubinemic infants in 2017. The three revised points are as follows: (i) newborns are classified under gestational age at birth or corrected gestational age, not birthweight; (ii) three treatment options were created: standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion; and (iii) initiation of standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion is decided based on the total serum bilirubin and serum unbound bilirubin reference values for gestational weeks at birth at <7days of age, and on the reference values for corrected gestational age at ≥7days of age. Studies are needed to establish whether chronic bilirubin encephalopathy can be prevented using the 2017 revised Kobe University treatment criteria for preterm infants in Japan.

Hyperbilirubinemia-induced pro-angiogenic activity of infantile endothelial progenitor cells

ObjectivesBilirubin, a by-product of heme degradation, is suggested to have a role for vascular protection. There is increasing evidence that bilirubin may directly affect the function and secretory activity of endothelial cells. In this study, potential effect of hyperbilirubinemia on biological features of circulation endothelial progenitor cells (cEPCs) isolated from infants was investigated. MethodsCirculation concentration, differentiation and migratory activity of cEPCs isolated from infants with (n = 111) or without (n = 73) hyperbilirubinemia were analyzed. Then, the potential beneficial effect of conditioned medium of cEPCs from infants with or without hyperbilirubinemia was examined on experimental mouse wounds. ResultsOur results revealed significantly higher percentages of cEPCs in infants with hyperbilirubinemia. Cell proliferation, and migratory properties of cEPCs isolated and expanded from infants with hyperbilirubinemia were significantly improved. Also, the conditioned medium of cEPCs from hyperbilirubinemic infants possessed a superior beneficial effect on wound healing, which was associated with increased protein levels of VEGF, IL-10, and Pho-ERK/ERK, and decreased TNF-α in the wound tissues. ConclusionsOur results showed that hyperbilirubinemia can activate migration, proliferating and angiogenic properties of cEPCs. Hyperbilirubinemia can promote the proangiogenic secretory activity of cEPCs, thereby resulting in enhancement of their regenerative wound healing properties.

Severe neonatal hyperbilirubinaemia is frequently associated with long hospitalisation for emergency care in Nigeria.

This study investigated the frequency and predictors of a long hospital stay (LHS) for severe neonatal hyperbilirubinaemia in Nigeria. Length of stay (LOS) for severe hyperbilirubinaemia was examined among neonates consecutively admitted to the emergency department of a children's hospital in Lagos from January 2013 to December 2014. The median LOS was used as the cut-off for LHS. Multivariate logistic regression determined the independent predictors of LHS based on demographic and clinical factors significantly associated with the log-transformed LOS in the bivariate analyses. We enrolled 622 hyperbilirubinaemic infants with a median age of four days (interquartile range 2-6 days) and 276 (44.4%) had LHS based on the median LOS of five days. Regardless of their birth place, infants were significantly more likely to have LHS if they were admitted in the first two days of life (p = 0.008) - especially with birth asphyxia - or had acute bilirubin encephalopathy (p = 0.001) and required one (p = 0.020) or repeat (p = 0.022) exchange transfusions. Infants who required repeat exchange transfusions had the highest odds for LHS (odds ratio 4.98, 95% confidence interval 1.26-19.76). Severe hyperbilirubinaemia was frequently associated with long hospitalisation in Nigeria, especially if neonates had birth asphyxia or required exchange transfusions.

The impact of hemoglobin on the efficacy of phototherapy in hyperbilirubinemic infants.

BackgroundPhototherapy is the routine treatment for neonatal hyperbilirubinemia. Absorption of light in the skin transforms the native Z,Z-bilirubin to photobilirubins. This study investigates whether the hemoglobin concentration has an impact on efficacy of phototherapy, expressed by the decline of total serum bilirubin concentration (TsB).MethodsA trial was conducted on 93 infants, gestational age ≥33 weeks, with uncomplicated hyperbilirubinemia. The infants were treated with conventional phototherapy using LED light for 24 h. The median light irradiance was 66.8 μW/cm2/nm.ResultsThe median decrease in TsB after 24 h was 121 (57-199) μmol/l; the median hemoglobin was 12.0 (7.0-14.7) mmol/l. There was a significant effect of hemoglobin concentration on the decrease in TsB of -3.61 μmol/mmol hemoglobin (P=0.022), after adjusting for initial TsB and postnatal age. That is, assuming the same initial TsB and postnatal age, for each mmol/l increase in hemoglobin, the decrease in TsB was 3.61 μmol/l smaller. In our hemoglobin range, the decrease in TsB is reduced by 28 μmol/l (23%).ConclusionIncreasing hemoglobin levels led to a decrease in the efficacy of phototherapy. Our data provide additional support for the conclusion that the transformation of bilirubin to photobilirubins takes place mainly in the superficial capillaries of the skin.

Update on Predicting Severe Hyperbilirubinemia and Bilirubin Neurotoxicity Risks in Neonates.

Extreme hyperbilirubinemia and kernicterus, though rare, continue to occur despite the adoption of universal screening. Unless they are known to have glucose-6-phosphate dehydrogenase deficiency, infants who currently develop kernicterus in high resource countries are often otherwise healthy newborns discharged from the well-baby nursery. In this review, we highlight risk factors that increase the risk of a newborn ≥35 weeks gestational age developing severe hyperbilirubinemia, as well as the risk factors that increase the hyperbilirubinemic infant's risk of kernicterus.

Bone measurements of infants with hyperbilirubinemia by quantitative ultrasound: the influence of phototherapy

Objective: The purpose of the current study was to investigate the possible effects of phototherapy on bone status of term infants evaluated by measurement of tibial bone speed of sound (SOS).Materials and methods: The phototherapy group (n = 30) consisted of children who had undergone phototherapy for at least 24 h and the control group (n = 30) comprised children who had not received phototherapy. Blood samples were obtained from all infants for serum calcium, phosphorus, magnesium, alkaline phosphatase, parathyroid hormone and vitamin D concentrations. The left tibial quantitative ultrasound (QUS) measurements were performed using a commercial device.Results: There was no statistically significant difference between phototherapy-exposed and nonexposed infants in terms of Ca, P, ALP, PTH and vitamin D levels. Comparison of bone SOS between the phototherapy-exposed and control group revealed no statistically difference. Also, no significant difference in Z-score for SOS was observed between those with or without exposure.Conclusion: The data of our study indicate that phototherapy treatment has no impact on bone status in the hyperbilirubinemic infants. Although there is no statistically significant evidence of an excess risk of bone damage following phototherapy, studies with larger sample sizes and longer duration of follow-up are needed to gain a better understanding of its effects.

Auditory Brainstem Response Improvements in Hyperbillirubinemic Infants

Background and ObjectivesHyperbillirubinemia in infants have been associated with neuronal damage including in the auditory system. Some researchers have suggested that the bilirubin-induced auditory neuronal damages may be temporary and reversible. This study was aimed at investigating the auditory neuropathy and reversibility of auditory abnormalities in hyperbillirubinemic infants.Subjects and MethodsThe study participants included 41 full term hyperbilirubinemic infants (mean age 39.24 days) with normal birth weight (3,200-3,700 grams) that admitted in hospital for hyperbillirubinemia and 39 normal infants (mean age 35.54 days) without any hyperbillirubinemia or other hearing loss risk factors for ruling out maturational changes. All infants in hyperbilirubinemic group had serum bilirubin level more than 20 milligram per deciliter and undergone one blood exchange transfusion. Hearing evaluation for each infant was conducted twice: the first one after hyperbilirubinemia treatment and before leaving hospital and the second one three months after the first hearing evaluation. Hearing evaluations included transient evoked otoacoustic emission (TEOAE) screening and auditory brainstem response (ABR) threshold tracing.ResultsThe TEOAE and ABR results of control group and TEOAE results of the hyperbilirubinemic group did not change significantly from the first to the second evaluation. However, the ABR results of the hyperbilirubinemic group improved significantly from the first to the second assessment (p=0.025).ConclusionsThe results suggest that the bilirubin induced auditory neuronal damage can be reversible over time so we suggest that infants with hyperbilirubinemia who fail the first hearing tests should be reevaluated after 3 months of treatment.

Multiple Genetic Modifiers of Bilirubin Metabolism Involvement in Significant Neonatal Hyperbilirubinemia in Patients of Chinese Descent.

The potential for genetic variation to modulate neonatal hyperbilirubinemia risk is increasingly being recognized. A case-control study was designed to assess comprehensive contributions of the multiple genetic modifiers of bilirubin metabolism on significant neonatal hyperbilirubinemia in Chinese descendents. Eleven common mutations and polymorphisms across five bilirubin metabolism genes, namely those encoding UGT1A1, HMOX1, BLVRA, SLCO1B1 and SLCO1B3, were determined using the high resolution melt (HRM) assay or PCR-capillary electrophoresis analysis. A total of 129 hyperbilirubinemic infants and 108 control subjects were evaluated. Breastfeeding and the presence of the minor A allele of rs4148323 (UGTA*6) were correlated with an increased risk of hyperbilirubinemia (OR=2.17, P=0.02 for breastfeeding; OR=9.776, P=0.000 for UGTA*6 homozygote; OR=3.151, P=0.000 for UGTA*6 heterozygote); whereas, increasing gestational age and the presence of –TA7 repeat variant of UGT1A1 decreased the risk (OR=0.721, P=0.003 for gestational age; OR=0.313, P=0.002 for heterozygote TA6/TA7). In addition, the SLCO1B1 and SLCO1B3 polymorphisms also contributed to an increased risk of hyperbilirubinemia. This detailed analysis revealed the impact of multiple genetic modifiers on neonatal hyperbilirubinemia. This may support the use of genetic tests for clinical risk assessment. Furthermore, the established HRM assay can serve as an effective method for large-scale investigation.

English

OBJECTIVE: Jaundice is a common finding in neonates affecting 70% of term and 80% of preterm neonates during the first week of life. So the objective of this study is to evaluate auditory and brainstem responses in hyper bilirubinemic infants and to see if there is any statistically significant increase in latencies of wave I and V waves. To initiate rehabilitative procedure as early in life as possible a screening method to detect auditory disabilities in hyper bilirubinemic infants is of great importance. So the present study is done to know the incidence of hearing loss in hyper bilirubinemic infants & to evaluate the waves I and V in those subjects. METHODS: 45 Infants with hyper bilirubinemia>12mg% & with no other risk factor who visited pediatric OPD of Bapuji Child Health Centre were evaluated using RMS EMG. EP MARK -II machine. Latencies of Waves I and V and interpeak latency of I-V were recorded. RESULTS: On one sample t-test, latency of wave I and IPL I-V were significantly increased (p-value <0.001), latency of V was prolonged which was statistically significant (p-value <0.01). Hearing impairment in the affected infants and complete deafness where none of the waves were recorded signify that it is a risk factor for deafness. CONCLUSION: Since hyper bilirubinemia is a risk factor for hearing impairment, their hearing screening by BERA at the earliest will help in their earliest initiation of rehabilitation when the brain is sensitive to the development of speech & language.

Is it Accurate to Separate Glucose-6-Phosphate Dehydrogenase Activity in Neonatal Hyperbilirubinemia as Deficient and Normal?

The aim of this study was to investigate glucose 6-phosphate dehydrogenase (G6PD) activity in term and late preterm babies with severe neonatal hyperbilirubinemia and its relationship to the severity and treatment of this disorder, regardless of level of G6PD activity (deficient/normal). A total of 529 term and late preterm (≥35 weeks) infants (228 female, 301 male) who were diagnosed with severe hyperbilirubinemia were included in this study. In each case, serum was collected to evaluate blood group, direct Coombs' test, complete blood cell count, total and direct bilirubin, thyroid-stimulating hormone, and G6PD activity. A partial correlation analysis was carried out to assess the relationship between G6PD activity and total bilirubin levels. A significant correlation was found between the severity of hyperbilirubinemia and G6PD activity in both males and females. Male neonates who had G6PD levels <12U/g Hb required more phototherapy time than neonates who had G6PD levels ≥12U/g Hb; and female neonates who had G6PD levels <16U/g Hb required more phototherapy time than neonates who had G6PD levels ≥16U/g Hb (p<0.0001). When we analyzed only breastfed infants, a significant difference also emerged in both sexes. Decreased G6PD activity was associated with increased phototherapy time and the need for exchange transfusion. Routine checks of G6PD level in hyperbilirubinemic neonates are very important in providing proper medical management to prevent bilirubin-induced neurological dysfunction. Appropriate identification of G6PD (<12U/g Hb for male infants and <16U/g Hb for female infants) raises awareness of the severity of the condition and the necessity for immediate care of severe hyperbilirubinemic infants.

UGT1A1, SLCO1B1, and SLCO1B3 polymorphisms vs. neonatal hyperbilirubinemia: is there an association?

Jaundice is a physiological phenomenon; however, severe hyperbilirubinemia occurs in only 5 to 6% of the healthy newborn population. It has been suggested that genetic variation could enhance the risk of hyperbilirubinemia when coexpressed with other icterogenic conditions. The study included newborns with a gestational age of greater than 35 wk and weights greater than 2,000 g with indications for phototherapy. The polymorphisms from UGT1A1 (rs8175347), SLCO1B1 (rs4149056 and rs2306283), and SLCO1B3 (rs17680137 and rs2117032) were analyzed by capillary electrophoresis and hydrolysis probes. A total of 167 hyperbilirubinemic infants and 247 control subjects were enrolled. The gender, ABO incompatibility, birth weight, and gestational age differed between the groups, but the allelic and genotypic frequency of the polymorphisms from SLCO1B genes did not. In logistic regression, the ABO incompatibility, gestational age, and polymorphic T allele of rs2117032 remained in the model. The presence of this polymorphism seemed to provide protection from hyperbilirubinemia. The individuals who were homozygous for the G allele of rs2306283 and who were glucose 6-phosphate-dehydrogenase deficient were more frequent among the cases. Although genetic variation accounts for a good part of this condition, the association between different polymorphisms and environmental factors has yet to be explained.

Neonatal hyperbilirubinemia and Gly71Arg mutation of UGT1A1 gene: a Chinese case–control study followed by systematic review of existing evidence

To determine whether the UDP-glucuronosyltransferase 1A1 gene (UGT1A1) Gly71Arg (211G>A) mutation is associated with neonatal hyperbilirubinemia. The study consisted of two parts. The case-control study included 112 hyperbilirubinemic infants and 105 control subjects from the Fifth People's Hospital of Shenzhen. Polymerase chain reaction, restriction fragment length polymorphisms and agarose gel electrophoresis techniques were used to detect the UGT1A1 211G>A mutation. Meta-analyses was performed to assess the association between neonatal hyperbilirubinemia and UGT1A1 211G>A. Our case-control study revealed that the likelihood of developing neonatal hyperbilirubinemia was 2.65 times higher in the infants with the A allele in the UGT1A1 211G>A than in the infants with the G allele (95% CI, 1.60-4.39). Meta-analyses (including data from our study) revealed that UGT1A1 211G>A is associated with an increased risk of neonatal hyperbilirubinemia [odds ratio (OR), 2.37; 95% CI, 2.05-2.74]. In the subgroup analyses based on ethnicity, significantly elevated risks were found in Asian populations (OR, 2.45; 95% CI, 2.10-2.84), but no significant associations were present in Caucasian populations (OR, 1.54; 95% CI, 0.87-2.75). The UGT1A1 211G>A mutation is associated with neonatal hyperbilirubinemia in Asians, but not in Caucasians.

Comparison of total oxidant/antioxidant status in unconjugated hyperbilirubinemia of newborn before and after conventional and LED phototherapy: A prospective randomized controlled trial

We evaluated and compared the oxidant and antioxidant status of hyperbilirubinemic infants before and after the two forms of phototherapy: conventional and LED phototherapy, in order to identify the optimal treatment method. Thirty newborns exposed to conventional (Group I) phototherapy and 30 infants exposed to LED phototherapy (Group II) were studied. The serum total antioxidant capacity (TAC) and the total oxidant status (TOS) were assessed by EREL's method. There were no statistically significant differences in TAC or TOS levels between Group I and Group II prior to phototherapy, and no statistically significant difference in TAC levels between the two groups after phototherapy; however, TOS levels were significantly lower in Group II compared to Group I after phototherapy. Oxidative stress index (OSI) increased after conventional phototherapy (p < 0.05) The increase in TOS following conventional phototherapy was not not observed following LED phototherapy. This difference should be considered when using phototherapy.

Assessment of DNA damage and plasma catalase activity in healthy term hyperbilirubinemic infants receiving phototherapy

Phototherapy (PT) is the most widely used form of treatment for unconjugated hyperbilirubinemia. One possible harmful consequence of PT is of a genetic nature. High levels of bilirubin may lead to oxidative damage in newborns: photochemical reactions may produce toxic photoproducts, probably peroxides. In order to investigate this hypothesis further under in vivo conditions, DNA strand-break frequency was examined by means of the comet assay in peripheral lymphocytes of icteric newborns undergoing PT treatment, and the levels of catalase, an antioxidant enzyme, were determined. We analyzed 20 term non-hemolitic hyperbilirubinemic jaundiced neonates before PT (‘before PT’ group) and just prior to ending PT (‘after PT’ group) and compared comet scores of these patients with those of 20 healthy term neonates who all had bilirubin levels in the physiological range. Comet scores (tail length, tail moment and %DNA in tail) of the group ‘before phototherapy’ were 23.5 ± 16.3, 7.41 (0.97–40.7), 33.0 ± 12.1, respectively and scores of after phototherapy group were 3.2 ± 1.8, 0.29 (0.3–3.2), 10.7 ± 3.7, respectively. Comet scores of the control group were 3.0 ± 2.9, 0.25 (0.03–3.22), 10.9 ± 4.5, respectively. Comet scores and plasma catalase activities in hyperbilirubinemic newborns were significantly higher before phototherapy, compared with the values after phototherapy and in the control groups ( p < 0.001). There was no statistical difference between the ‘after phototherapy’ group and the controls ( p > 0.05). These results indicate that high serum bilirubin level has genotoxic effects as is evident from the high rate of DNA strand-breaks in jaundiced newborns. Also PT does not cause an increase in DNA oxidation or induce the genotoxic effects of bilirubin. The counteracting effect of higher catalase activities in hyperbilirubinemic newborns may be responsible for the inactivating toxic and DNA-damaging effects of PT.

Homozygous variant of UGT1A1 gene mutation and severe neonatal hyperbilirubinemia

The aim of the present study was to compare, in a case-control study, the prevalence of nucleotide 211 guanine to adenine (G-->A) mutation of uridine diphosphoglucuronosyl transferase (UGT1A1) gene in Malaysian Chinese newborns with and without severe hyperbilirubinemia (total serum bilirubin >250 micromol/L during first 48 h of life or > or =300 micromol/L thereafter), and to determine whether this mutation was a significant risk factor associated with severe hyperbilirubinemia. Seventy-four term infants of Chinese descent admitted with severe hyperbilirubinemia were recruited. Infants without severe hyperbilirubinemia (n = 125) were randomly selected from among healthy Chinese term infants. UGT1A1 nucleotide 211 polymorphism was assayed using the Taqman single nucleotide polymorphism genotyping method. Using gestational age, types of feeds, G6PD mutation, G6PD enzyme levels, and UGT1A1 gene mutation status as independent variables, logistic regression analysis was carried out to determine the significant risk factors associated with severe hyperbilirubinemia. UGT1A1 gene mutation was significantly more common among hyperbilirubinemic infants (39.2%) than controls (25.6%; P = 0.04). Gestational age (adjusted odds ratio [OR], 0.7; 95% confidence intervals [CI]: 0.5-0.9; P = 0.01), G6PD mutation (adjusted OR, 7.2; 95%CI: 2.7-19.0; P < 0.0001), exclusive breast-feeding (adjusted OR, 11.7; 95%CI: 2.7-49.9; P = 0.001), and homozygous variant of UGT1A1 gene mutation (adjusted OR, 32.2; 95%CI: 3.8-273.2; P = 0.001) were significant risk factors. Heterozygous variant of UGT1A1 gene mutation, actual levels of G6PD enzyme, and mixed feeding were not. Homozygous variant of nucleotide 211 G-->A mutation of UGT1A1 gene is a significant risk factor associated with severe hyperbilirubinemia among Malaysian Chinese newborns.

Neonatal hyperbilirubinemia increases intestinal protein permeability and the prevalence of cow's milk protein intolerance

Bilirubin is a newly discovered modulator of the gut barrier in vitro and in vivo. We studied the effect of bilirubin on the serosal to mucosal intestinal permeability in vivo. We also investigated the prevalence of cow's milk protein intolerance (CMPI) in infants with moderate hyperbilirubinemia versus matched controls. Faecal alpha 1 antitrypsin (a1AT) was used to monitor intestinal protein loss; a large cohort was prospectively followed for 12 months for sign and symptoms of CMPI. Neonates with hyperbilirubinemia had higher stool excretion of a1AT than controls (0.68 +/- 0.28 mg/g vs. 0.25 +/- 0.11 mg/g; p < 0.01). Faecal a1AT correlates with total serum bilirubin (TSB) (r = 0.85; p < 0.01). Also, in the first 12 months of life, formerly hyperbilirubinemic infants had an higher prevalence of CMPI (14/353 vs. 4/339; chi2= 4.018, p = 0.045). Neonatal hyperbilirubinemia increases stool protein loss and is also a mild risk factor for CMPI.