Risk Factors For Severe Hyperbilirubinemia Research Articles

Risk factors for severe hyperbilirubinemia and exchange transfusion in neonates

Background Neonatal jaundice is a common cause of neonatal admission to the hospital. The neonatal jaundice frequency has been increased last decade. 65% of term babies develop jaundice clinically in 1st week (in preterm babies 80%).Methods One hundred and sixty four neonates with severe hyperbilirubinemia, were enrolled in this study. Most important relevant informative data was taken during admission to the hospital. American Academy of Pediatrics (AAP) guidelines were applied in management of the patients, which was been either phototherapy or exchange transfusion with phototherapy ResultsMeanTSB level of 164 cases was 16.6mg/dl. TSB was significantly high in the male, with Rh-ve mothers and Rh+ve babies, more than 37weeks gestational age, admitted after 72 hours of life, were having history of previous siblings affected with jaundice and or received phototherapy and family history of hemolytic diseases. Phototherapy alone was used as treatment modality in most of the patients. On admission to the NCU, the mean age of the infants who needed exchange transfusion 4.97 ±2.24 while the mean TSB level was 20.2±2.84 mg/dL. The most common cause for ET was early discharge from the maternity unit & late admission to the NCU 72.4%. ConclusionsSevere hyperbilirubinemia was been more common in male neonates, > 37weeks of gestational age, with Rh-ve mothers and Rh+ve babies, who admitted after 72hrs of life, . Most of cases treated by phototherapy. The most common cause for ET was early discharge from the maternity unit & late admission to the NCU.

Statistical model for prediction of ABO hemolytic disease of the fetus and newborn inIndia.

Abstract ABO incompatibility is the most common cause of immune hemolytic disease of the fetus and newborn (HDFN). The American Academy of Pediatrics lists blood group incompatibility as one of the major risk factors for severe hyperbilirubinemia in newborns. We have estimated the risk of ABO HDFN to determine the need for its routine screening. Blood group data from all blood donors who donated in the last 10 years were collected and analyzed. The population prevalence of ABO blood group genes using the phenotype data of blood donors was estimated. This information was further used to calculate an incidence of ABO HDFN requiring intervention in the population. ABO blood group typing was analyzed in 425,743 blood donors. The ABO phenotypes of A, B, O, and AB were 22.48, 36.73, 31.59, and 9.2 percent, respectively. The gene frequencies were 0.1733, 0.2647, and 0.5620 for A, B, and O, respectively. It was estimated that 13.84 percent of group O women would give birth to a non–group O baby and that approximately 2.77 percent of deliveries would likely have ABO HDFN in the study population. In India, the estimated risk of ABO HDFN is 2.9 percent, with a daily 2196 babies at risk of ABO HDFN requiring intervention. This analysis estimates the overall burden of ABO HDFN in the population, which could aid in the decision-making of policymakers, physicians, and community health practitioners to improve neonatal care.

Severe neonatal hyperbilirubinemia in the southeast region of Turkey

Severe neonatal hyperbilirubinemia is an important cause of morbidity and mortality in developing countries. The aim was to assess etiologic reasons for development of severe hyperbilirubinemia and define risk factors for exchange transfusion and acute bilirubin encephalopathy (ABE) in Şanlıurfa located in the southeast region of Turkey. An observational cohort study included 115 infants with ≥35 weeks of gestation admitted with diagnosis of severe hyperbilirubinemia in a period of 18 months. Potential risk factors associated with exchange transfusion and development of ABE were analyzed. Among 115 infants, 67 (58.3%) received exchange transfusion and 45 (39.1%) developed ABE. Rh isoimmunization (OR: 24.6, 95% CI = 2.2–271, P = 0.009), glucose-6-phosphate dehydrogenase deficiency (G6PD) (OR: 21.1, 95% CI = 1.8–238.4, P = 0.01), early discharge (OR: 14.4, 95% CI = 4.2–48.9, P ≤ 0.001), and male sex (OR: 4.3, 95% CI = 1.3–14.1, P = 0.02) were independently associated with an increased risk for exchange transfusion. Being a refugee (OR: 6.8, 95% CI = 1.8–25.8, P = 0.005) and G6PD deficiency (OR: 9.9, 95% CI = 1.3–71.9, P = 0.02) were associated with development of ABE. Early discharge, Rh isoimmunization, and G6PD deficiency are significant risk factors for severe hyperbilirubinemia and exchange transfusion. Prevention of early hospital discharges, family education to increase awareness for hazardous effects of hyperbilirubinemia, and early follow-up visits after discharge would reduce the disease burden.

Evaluation of Risk Factors for Exchange Range Hyperbilirubinemia and Neurotoxicity in Neonates from Hilly Terrain of India.

Background and Aim:Neonatal hyperbilirubinemia continues to be the most common cause of hospital admissions and readmissions in the neonatal population worldwide and this pattern continues despite attempts to identify neonates at risk of pathological hyperbilirubinemia. Therefore, this study aimed to study the risk factors for severe hyperbilirubinemia in neonates.Materials and Methods:An observational prospective study was undertaken for 1 year in neonates with hyperbilirubinemia requiring double volume exchange transfusion in neonatology unit of a tertiary rural health care hospital.Results:Risk factors included ABO incompatibility in 14 (28.5%), Rh incompatibility in 14 (28%). Other risk factors for hyperbilirubinemia were, jaundice in elder sibling, oxytocin use, birth asphyxia, hypothyroidism, ABO along with Rh incompatibility, Glucose-6 phosphate Dehydrogenase deficiency, cephalhematoma, and sepsis in neonates. Ten (20%) neonates were neurologically abnormal with signs of encephalopathy. Significant association of risk factors with neurotoxicity were also found. All neurologically abnormal neonates were small for date and none was appropriate for date (P = 0.05). There were no neurologically abnormal neonates with A+ and O− mothers (P = 0.04).Conclusion:The high rate of exchange transfusion warrants aggressive management of neonatal hyperbilirubinemia by health-care providers by adequate dissemination of information, strict following of hour-based normograms, performing total serum bilirubin assessment in all icteric neonates, and stratification into risk groups thereafter.

Risk factors for severe neonatal hyperbilirubinemia in low and middle-income countries: a systematic review and meta-analysis.

BackgroundAvailable evidence suggests that low- and middle-income countries (LMICs) bear the greatest burden of severe neonatal hyperbilirubinemia characterized by disproportionately high rates of morbidity, mortality and neurodevelopmental disorders compared to high-income countries. We set out to identify the risk factors that contribute to the burden of severe hyperbilirubinemia in the most developmentally disadvantaged LMICs to highlight areas for action and further research.MethodsWe systematically searched PubMed, Scopus, Ovid EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), WHO Library Database (WHOLIS), African Index Medicus (AIM), African Journals Online (AJOL), LILACS, and IndMed for reports published between January 1990 and June 2014. We included only studies that controlled for the effects of confounding variables in determining maternal and infant risk factors for severe hyperbilirubinemia. We conducted meta-analysis of the eligible studies and computed the summary risk estimates with random effects models.ResultsA total of 13 studies with 1,951 subjects and 32,208 controls from India, Nigeria, Pakistan, Nepal and Egypt were identified and analyzed. The pooled data showed that primiparity (OR, 1.59; 95% CI:1.26-2.00), delivery outside public hospitals (OR, 6.42; 95% CI:1.76-23.36), ABO incompatibility (OR, 4.01; 95% CI:2.44-6.61), Rhesus hemolytic disease (OR, 20.63; 95% CI:3.95-107.65), G6PD deficiency (OR, 8.01; 95% CI:2.09-30.69), UGT1A1 polymorphisms (OR, 4.92; 95% CI:1.30-18.62), low gestational age (OR, 1.71; 95% CI:1.40-2.11), underweight/weight loss (OR, 6.26; 95% CI:1.23-31.86), sepsis (OR, 9.15; 95% CI:2.78-30.10) and high transcutaneous/total serum bilirubin levels (OR, 1.46; 95% CI:1.10-1.92) placed infants at increased risk of severe hyperbilirubinemia or bilirubin induced neurologic dysfunctions. Low social class was not associated with an increased risk of severe hyperbilirubinemia.ConclusionsInfants at risk of severe hyperbilirubinemia in LMICs are associated with maternal and neonatal factors that can be effectively addressed by available interventions to curtail the disease burden prevailing in the affected countries.

International Perspectives

After completing this article, readers should be able to: 1. Describe the unique characteristics of neonatal jaundice in Chinese infants. 2. Describe the major findings from a recent epidemiological survey of bilirubin encephalopathy or kernicterus in China. 3. Understand the primary causes and current problems for decreasing the incidence of bilirubin encephalopathy or kernicterus in China. 4. Outline future directions for obtaining population based data on bilirubin encephalopathy or kernicterus and formulating optimal management of neonatal jaundice. Hyperbilirubinemia is the number one reason for neonatal admission in most Chinese neonatal units. Early severe neonatal hyperbilirubinemia, resulting in bilirubin encephalopathy, may cause kernicterus, with residual hearing loss, cerebral palsy, neurodevelopmental disabilities, and other complications. It inflicts a heavy burden on both families and society. With the use of phototherapy, exchange transfusion, and other treatment technologies, kernicterus became less common, but an upward trend in incidence has been observed in recent years. China's large population, the very uneven distribution of medical resources between regions, and Asians being at high risk for hyperbilirubinemia suggest that the incidence of bilirubin encephalopathy and kernicterus should be higher than that in Western countries. Because of the lack of large-sample epidemiological surveys and population-based disease reporting systems, the specific incidence is not clear. In 1998, Yeung (1) summarized the characteristics of neonatal jaundice in China: 1) high unconjugated hyperbilirubinemia causing neonatal jaundice is particularly prevalent in South China; 2) he believes there is a “Chinese nonspecific neonatal jaundice” characterized by the clinical jaundice being more severe and longer lasting and having a delayed peak that occurs after the fourth day; 3) hemolytic disease of the newborn due to ABO incompatibility is the most common form of hemolytic jaundice; 4) in neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency, an acute bilirubin encephalopathy can appear late in the neonatal period; and 5) resolution of …

Hyperbilirubinemia in breastfed term neonates

Dear Editor: I read with great interest the article by Chen et al. [3]. The authors conducted a study to identify risk factors associated with jaundice in exclusively breastfed term neonates and to guide clinicians regarding the management. The following points need some comment. The authors found the overall hyperbilirubinemia rate (≥15.0 mg/dl) of 35.3%. This rate is much higher than that described previously, in which the authors found 12% to 13% of breastfed babies with a bilirubin level of ≥12 mg/dl [4, 5]. The possible explanations are as follows. The hyperbilirubinemic group had significantly higher TcB levels at nursery discharge and at OPD follow-up in the present study. Other risk factors for severe hyperbilirubinemia not reported in the present study are: blood group incompatibility, G6PD deficiency, previous sibling received phototherapy, male sex, infant of diabetic mother, East Asian race, etc. [1]. Besides these, supplementary feeding, weight loss percentage, and birth trauma significantly increase the risk of jaundice [2]. The description of length of stay in the nursery not being a major risk factor for hyperbilirubinemia in exclusively breastfed infants might not be true, as the authors have not excluded the above-reported risk factors. The current guideline suggests discharge at any time <72 h significantly increases the risk for readmission to hospital and the risk for readmission with hyperbilirubinemia [1]. The authors also reported that a cesarean section cannot protect breastfed newborn infants from developing hyperbilirubinemia based on their observation. This might be true, as breastfeeding is often delayed in these infants due to the effect of pain and anesthesia in the mother, as well as other comorbidities for which cesarean section was performed. To conclude, risk factors for jaundice in breastfed infants need to be clearly defined, so that affected infants can be diagnosed early and given timely treatment.

Hyperbilirubinemia in the Newborn

After completing this article, readers should be able to: 1. List the risk factors for severe hyperbilirubinemia. 2. Distinguish between physiologic jaundice and pathologic jaundice of the newborn. 3. Recognize the clinical manifestations of acute bilirubin encephalopathy and the permanent clinical sequelae of kernicterus.4. Describe the evaluation of hyperbilirubinemia from birth through 3 months of age. 5. Manage neonatal hyperbilirubinemia, including referral to the neonatal intensive care unit for exchange transfusion.

Severe Neonatal Hyperbilirubinemia and Adverse Short-Term Consequences in Baghdad, Iraq

Background: Severe neonatal hyperbilirubinemia, when unmonitored or untreated, can progress to acute bilirubin encephalopathy (ABE). Initiatives to prevent and eliminate post-icteric sequelae (kernicterus) are being implemented to allow for timely interventions for bilirubin reduction. Objectives: We report an observational study to determine the clinical risk factors and short-term outcomes of infants admitted for severe neonatal jaundice. Methods: A post-discharge medical chart review was performed for a cohort of infants admitted for management of newborn jaundice to the Children Welfare Teaching Hospital during a 4-month period in 2007 and 2008. Immediate outcomes included severity of hyperbilirubinemia, association of ABE, need and impact of exchange transfusion, and survival. Short-term post-discharge follow-up assessed for post-icteric sequelae. Results: A total of 162 infants were admitted for management of severe jaundice. Incidences of severe sequelae were: advanced ABE (22%), neonatal mortality within 48 h of admission (12%) and post-icteric sequelae (21%). Among the cohort, 85% were <10 days of age (median 6 days, IQR 4–7 days). Readmission total serum bilirubin ranged from 197 to 770 µM; mean 386 ± 108 SD µM (mean 22.6 ± 6.3 SD mg/dl; median 360, IQR 310–445 µM). The major contributory risk factor for the adverse outcome of kernicterus/death was admission with advanced ABE (OR 8.03; 95% CI 3.44–18.7). Other contributory factors to this outcome, usually significant, but not so for this cohort, included home delivery, sepsis, ABO or Rh disease. Absence of any detectable signs of ABE on admission and treatment of severe hyperbilirubinemia was associated with no adverse outcome (OR 0.34; 95% CI 0.16–0.68). Conclusions: Risks of mortality and irreversible brain injury among healthy infants admitted for newborn jaundice are urgent reminders to promote education of communities, families and primary health care providers, especially in a fractured health system. Known risk factors for severe hyperbilirubinemia were overwhelmed by the effect of advanced ABE.

Genetic Factors Influencing Severe Atazanavir‐Associated Hyperbilirubinemia in a Population with Low UDP‐Glucuronosyltransferase 1A1*28 Allele Frequency

High prevalence of severe atazanavir-associated hyperbilirubinemia in Asians with low prevalence of the UDP-glucuronosyltransferase (UGT)1A1*28 polymorphism suggests the importance of genetic factors other than UGT1A1*28 for atazanavir-associated hyperbilirubinemia in these populations. Serum bilirubin levels were measured in 129 Korean human immunodeficiency virus-infected patients 3 months after initiation of atazanavir (400 mg per day) with good adherence to medication. The multidrug resistance gene 1 (MDR1) C3435T and G2677T/A variations and UGT1A1*6 and *28 were examined by direct sequencing of DNA from peripheral whole blood samples. The associations between genetic polymorphisms and severe (grade 3-4) hyperbilirubinemia were evaluated using multivariate logistic regression analysis including demographic and clinical variables. The median patient age was 39 years (interquartile range, 34-51 years), and 91% were men. At baseline, the median CD4 cell count was 261 cells/microL (interquartile range, 181-405 cells/microL). Severe hyperbilirubinemia was detected in 27 patients (21%). The independent risk factors for severe hyperbilirubinemia were low baseline CD4 cell count (adjusted odds ratio per 10 cells/microL increase, 0.97; 95% confidence interval, 0.94-0.99), UGT1A1*28 (adjusted odds ratio, 4.15; 95% confidence interval, 1.46-11.84), and MDR1 G2677T/A (adjusted odds ratio, 9.65; 95% confidence interval, 1.09-85.61). Of 19 patients with wild-type alleles for both MDR1 2677 and UGT1A1*28, none developed severe hyperbilirubinemia. The MDR1 G2677T/A variation and UGT1A1*28 are independent risk factors for severe atazanavir-associated hyperbilirubinemia in Korean human immunodeficiency virus-infected patients.

False-negative results of pre-discharge neonatal bilirubin screening to predict severe hyperbilirubinemia: a need for caution

Routine bilirubin screening prior to newborn hospital discharge, using an hour-specific bilirubin nomogram, has been advocated to assess risk for subsequent severe hyperbilirubinemia. However, the false-negative rate has never been adequately studied. Our objective was to determine false-negative results of pre-discharge bilirubin screening. After routine pre-discharge, bilirubin screening was in place for over 4 years, we performed a retrospective chart review to identify infants readmitted for total bilirubin levels > 17 mg/dl (>290.7 micromol/l). We documented each infant's pre-discharge bilirubin level, risk-zone assignment by nomogram, the presence or absence of risk factors for severe hyperbilirubinemia, co-morbidities upon readmission, treatment received, and ultimate disposition. Readmitted infants whose pre-discharge bilirubin was in the low-risk (<40th percentile) and low-intermediate (40-75th percentile) risk zones of the nomogram, were considered false-negatives. Of the 6,220 infants discharged from the newborn nursery during the 51-month study period, 28 (0.45%) were readmitted for treatment of serum bilirubin levels > 17 mg/dl (>290.7 micromol/l). All received phototherapy and none required exchange transfusion. Pre-discharge bilirubin values were <40th percentile (low-risk zone) in one infant (3.6%), and between 40-75th percentiles (low-intermediate risk zone) in twelve infants (43%). Risk factors for the development of severe hyperbilirubinemia were present in 27 (96%) readmitted infants. In conclusion, nearly half of readmitted infants had pre-discharge bilirubin values in zones considered at lower risk. The use of pre-discharge bilirubin screening alone to assign future risk for severe hyperbilirubinemia may provide false reassurance. Rigorous research is required to determine the test characteristics of pre-discharge bilirubin screening before widespread acceptance and implementation. Universal early post-discharge follow-up should remain the cornerstone of preventing severe hyperbilirubinemia.

Risk Factors for Severe Hyperbilirubinemia among Infants with Borderline Bilirubin Levels: A Nested Case-Control Study

To estimate the effect of phototherapy and other predictors on the risk of total serum bilirubin (TSB) >or= 25 mg/dL in infants with a TSB of 17 to 22.9 mg/dL at age >or= 48 hours. From a cohort of 285295 infants >or= 34 weeks gestation and >or= 2000 g born between 1995 and 2004 in northern California Kaiser hospitals, we identified 17986 with a TSB of 17 to 22.9 mg/dL at age >or= 48 hours. All infants exhibiting a TSB >or= 25 mg/dL were selected as cases for the study. Four randomly selected controls were matched to each case based on the difference between their qualifying TSB and the American Academy of Pediatrics' phototherapy threshold. A total of 62 cases were identified (0.4%). Six of these (10%) received inpatient phototherapy within 8 hours, along with 101 controls (41%) (adjusted odds ratio [AOR] 0.15; 95% confidence interval [CI] 0.06 to 0.40). Cases more often had lower gestational age (AOR 3.24; 95% CI 1.24 to 8.47 for 38 to 39 weeks and AOR = 3.70; 95% CI 0.61 to 22.4 for 34 to 37 weeks compared with >or= 40-week infants), bruising, (AOR 2.52; 95% CI 1.16 to 5.50), exclusive breast-feeding (AOR 2.09; 95% CI 1.05 to 4.03), and TSB increase of >or= 6 mg/dL/day (AOR 2.39; 95% CI 1.18 to 4.85). Phototherapy was 85% effective in preventing TSB >or= 25 mg/dL. The strongest predictors of TSB >or= 25 mg/dL were gestational age, bruising, family history, and rapid rise in TSB.

Risk factors for severe hyperbilirubinemia in neonates.

The incidence of severe neonatal hyperbilirubinemia is higher in Asians than in whites. A case-control study was designed to investigate the effects of eight known risk factors [breast feeding, ABO incompatibility, premature birth, infection, cephalohematoma, asphyxia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and variant UDP-glucuronosyltransferase 1A1 (UGT1A1) gene] and a suspicious analog [organic anion transporter 2 (OATP 2) gene] on severe hyperbilirubinemia in Taiwanese neonates. The 72 study subjects and 100 hospital control subjects consisted of neonates with peak serum bilirubin levels > or =342 microM and <256.5 microM, respectively. The PCR-restriction fragment length polymorphism method was applied to detect the UGT1A1, OATP 2, and G6PD genes. The results of multivariate logistic regressions, adjusted for covariates, revealed odds ratios (ORs) of 4.64 [95% confidence interval (CI): 2.25-9.57; p < 0.001], 3.36 (95% CI: 1.54-7.35; p=0.002), and 3.02 (95% CI: 1.30-6.99; p=0.010) for neonates who were fed with breast milk, and carry the variant UGT1A1 gene at nucleotide 211 and the variant OATP 2 gene at nucleotide 388, respectively. The ORs, adjusted for covariates, for the other six risk factors were not statistically significant. The ORs in neonates who had one, two, and three significant risk factors were 8.46 (95% CI: 2.75-34.48; p < 0.001), 22.0 (95% CI: 5.50-88.0; p < 0.001), and 88.0 (95% CI: 12.50-642.50; p < 0.001), respectively. In conclusion, neonates who carry the 211 and 388 variants in the UGT1A1 and OATP 2 genes, respectively, as well as feed with breast milk are at high risk to develop severe hyperbilirubinemia.