Prevention Of Neonatal Hyperbilirubinemia Research Articles

Study of immunohematological and biochemical parameters in neonatal jaundice at tertiary care centre

Introduction: Jaundice is most common problem faced by neonates in the first week of life. Although physiological jaundice is more frequent as compared to pathological jaundice, so it is very important to differentiate between the two as pathological jaundice may lead to kernicterus and subsequently brain damage. There are various modalities of investigations for diagnosis of jaundice e.g. complete blood count, Total serum bilirubin, Blood group, Direct and Indirect coomb’s test, G-6PD deficiency etc. by which we can reach at diagnosis. Treatment is also dependent upon the amount of total serum bilirubin and various other laboratory investigations. Thus laboratory workup is very important for diagnosis, prevention of neonatal hyperbilirubinemia and its complications. With this background present study was conducted for the analysis of clinicopathological profile among infants with neonatal hyperbilirubinemia. Aims and Objectives: The current study was planned to assess the hematological profile of neonatal jaundice and to categorize it on the basis of causes and severity. Materials and Methods: The present study conducted on 140 neonates admitted in NICU, at tertiary care centre, Ahmedabad; during first week of life along with total serum bilirubin level greater than 5 mg/dl. Peripheral blood was drawn from all study subjects under aseptic precautions and study done for Total Serum bilirubin, Direct and indirect coomb’s test, Blood group, G-6PD deficiency, complete blood count and CRP. Results: In our study among 140 cases with neonatal jaundice, Total number of Pre-term babies (< 37 weeks) was 91 (65%). Most of the neonates were present with jaundice at the age of 2-4 days. Physiological jaundice constituted majority in 95 cases (67%). ABO incompatibility was the commonest cause of pathological jaundice followed by septicemia. The rise in total serum bilirubin level was found to be more in pathological jaundice as compare to physiological jaundice.

Risk Factors and Causes of Neonatal Hyperbilirubinemia: A Systematic Review Study

Context: Jaundice is a common problem and the most common risk factor for hospitalization during the neonatal period. Objective: The prevention of neonatal hyperbilirubinemia would not be possible without identifying its predisposing risk factors. The present systematic review study aims to determine the risk factors of neonatal jaundice. Data Sources: Databases including Science Direct, Cochrane Library, Web of Science (ISI), PubMed, and Google Scholar were searched to identify all eligible papers concerning the risk factors of neonatal hyperbilirubinemia. Study Selection: This systematic review was performed to review the causes and risk factors of neonatal hyperbilirubinemia. Finally, 18 articles were defined as eligible for further review. Data Extraction: The keywords included neonates, jaundice, hyperbilirubinemia, and risk factors. The inclusion criteria were studies determining jaundice risk factors, while papers with only published abstracts were excluded. Results: A total of 18 eligible articles (3 retrospective, 4 prospective, 10 cross-sectional, and 1 historical cohort) out of 421 retrieved articles were included in this review. The etiologic causes for neonatal jaundice were ABO incompatibility (24.6%), infection (including UTI and sepsis) (13.7%), G6PD deficiency (9.4%), Rh incompatibility (7%), and cephalohematoma (2.9%), while, known predisposing factors for neonatal jaundice included unknown (33.2%), low birth weight (30.9%), hyperbilirubinemia in siblings (22.7%), prematurity (20.1%), and infant of diabetic mother (6.7%). Conclusion: According to our review with considering the studies, the etiologic causes for neonatal jaundice are ABO incompatibility, infection (including UTI and sepsis), G6PD deficiency, Rh incompatibility, and cephalohematoma. While, known predisposing factors for neonatal jaundice include low birth weight, hyperbilirubinemia in siblings, prematurity, and infant of diabetic mother.

Effect of phototherapy on serum calcium level in neonatal jaundice

Objectives The aim of the study was to determine the effect of phototherapy on serum calcium level in neonatal jaundice. Background Phototherapy plays a significant role in the treatment and prevention of hyperbilirubinemia in neonates. However, this treatment modality may result in the development of some complications such as induction of hypocalcemia. Patients and methods This study included 50 full-term neonates with jaundice (25 males and 25 females) who received phototherapy for treatment of neonatal indirect hyperbilirubinemia and 25 neonates (13 males and 12 females) complaining of exaggerated physiological hyperbilirubinemia taken as control not exposed to phototherapy. Serum calcium was checked before and 48 h after starting phototherapy. A comparative study was conducted between these groups to determine the effect of phototherapy on serum calcium level. Results In the neonates of the study group, the serum bilirubin level before phototherapy was 15.48 ± 1.94 mg/dl. However, the serum bilirubin level after phototherapy was 12.41 ± 2.10 mg/dl. There was highly statistically significant decrease of the serum bilirubin levels after phototherapy as compared with serum bilirubin levels before phototherapy in the study group (P Conclusion Hypocalcemia is a common complication of phototherapy.

English

INTRODUCTION: Jaundice is most common problem faced by neonates in the first week of life. Although physiological jaundice is more frequent as compared to pathological jaundice it is very important to differentiate between the two as pathological jaundice may lead to kernicterus and subsequently brain damage. There are various modalities of investigations e.g. Serum bilirubin, Direct and indirect coomb's test, Blood group, G-6PD deficiency, reticulocyte count by which we can reach at diagnosis. Treatment is also dependent upon the amount of serum bilirubin and various other laboratory investigations. Thus laboratory workup is very important for diagnosis and prevention of neonatal hyperbilirubinemia in newborn. With this background present study was conducted to study the clinico- pathological profile among infants with neonatal hyperbilirubinemia. METHODOLOGY: A prospective study was carried out for the duration of 1 year in one of the teaching hospitals. RESULTS: Altogether 63 babies were enrolled in the study. Male babies out numbered the female (58.7% vs. 41.3%).Mean age of the study population was 2.97 days with standard deviation of 1.2 days. Percentage of Pre-term babies was 30.1. Neonates having low birth weight were 17(26.9%). Physiological jaundice constituted (40)62% cases of Neonatal hyperbilirubinemia. ABO incompatibility was the commonest cause of pathological jaundice followed by septicemia. Statistically significant rise in the serum bilirubin was noted in pathological jaundice as compared to physiological jaundice. C-reactive protein (CRP) was found to be positive in all the cases of septicemia. Direct and indirect Coomb's test was positive in all the cases with Rh incompatibility. CONCLUSION: Neonatal hyperbilirubinemia is associated with various other clinical morbidities. Causes of hyperbilirubinemia should be investigated comprehensively. ABO and Rh typing should be done along with Coombs Test, reticulocyte count and G6PD screening.

The Significance of Enterohepatic Circulation in the Causation Neonatal Hyperbilirubinemia

Sir, This is in reference to the study by Rana et al.[1] A robust triple-blind design, appropriate sample-size, and statistical methods–sensitivity analysis and effect-size estimation– employed by the authors could well make the investigation a landmark study evaluating the role of zinc in the prevention of hyperbilirubinemia in neonates. However, the study simultaneously conjures-up an important question about the role of enterohepatic circulation (EHC) in the causation of neonatal jaundice which may also have implications on the physiological doctrine for the intervention tested. Overproduction of bilirubin from heme is considered the most prevalent mechanism of neonatal hyperbilirubinemia apart from impaired uptake, conjugation, and EHC. We have limited instances where EHC is considered the prime mechanism for jaundice, e.g., pyloric stenosis, lower intestinal atresia, paralytic ileus, and meconium-plug-syndrome (virtually no removal of bilirubin due to distal obstruction). There is limited data to suggest that the resorption of bilirubin from the intestine can be a major cause of neonatal physiologic jaundice [2]. It has been stated that neonatal hyperbilirubinemia is exacerbated–if not caused–by enhanced bilirubin resorption through EHC [3]. In fact, more obvious than EHC, a markedly reduced UDP-glucuronyl transferase activity is noted in pyloric stenosis [3]. Enhanced EHC induced by human milk has a putative role in prolonging ‘breastmilk jaundice’ [4]. In the past, various strategies have been employed to counteract EHC with inconsistent results, in terms of the incidence and severity of jaundice [5]. Consequently, it is advised that such interventions are at the best used as an adjuvant, along with more established modalities like phototherapy [6]. The results of the present study by Rana et al., showing no significant reduction in the incidence of hyperbilirubinemia, requirement of phototherapy and mean STB (serum total bilirubin) at 72 h, are in line with the outcomes of previous studies employing other agents. Therefore, although past studies have suggested that EHC may play a significant role in the bilirubin metabolism, it appears less likely that EHC is a major cause of neonatal hyperbilirubinemia, though it may play some contributory role in prolonging physiological jaundice. Therefore, negative results of these studies probably have a bearing on the underlying doctrine of ‘prevention of hyperbilirubinemia by clogging-up EHC’, irrespective of the agent (agar, charcoal, cholestyramine or zinc) employed. Other limitations of the study were the use of nonstandardized oral zinc dose, lack of serum zinc level monitoring, inadequate reporting of the adequacy of breastfeeding and vomited and/or skipped doses, and delayed initiation of the intervention.

Oral Administration of Zinc Deuteroporphyrin IX 2,4 Bis Glycol Inhibits Heme Oxygenase in Neonatal Rats

Zinc deuteroporphyrin IX 2,4 bis glycol (ZnBG) has been shown to be a potent inhibitor of heme oxygenase (HO) in vitro. Oral administration, which has been minimally effective with other metalloporphyrins, could be clinically advantageous for prevention of neonatal hyperbilirubinemia. Therefore, we examined the effect of oral administration of ZnBG on tissue HO activity and tissue ZnBG concentrations. Suckling rats at 2 weeks of age received ZnBG at 40 mumol/kg BW via gastric gavage. Rats were killed with anesthetic over-dose after 60 min. ZnBG was detected in the portal and systemic circulation (n = 12), and the liver, kidney, spleen, and intestine (n = 8). ZnBG concentrations of 7.9 nmol/g liver and 1.7 nmol/g spleen corresponded to 67 and 72% inhibition of control HO activity (n = 9; p less than 0.0005) respectively.

`A New Era in Therapy for Hyperbilirubinemia"

The article by Kappas et al in this issue (pp 485-497) represents a promising and exciting new approach to the prevention of neonatal hyperbilirubinemia. This important advance is based on a decade of careful basic research before this first clinical study in infants was carried out. Pediatricians have long dreamed of the day when the bilirubin problem would be solved and they would be free of the constant worry about "what to do for a certain level of serum bilirubin." There is an ancient Chinese proverb: "A journey of a thousand miles begins with a single step." Kappas et al have taken that step.

Prevention of neonatal hyperbilirubinemia in rhesus monkeys by tin-protoporphyrin.

Rhesus monkey infants were injected subcutaneously at birth with 12 to 100 mumol of tin-protoporphyrin IX, a competitive inhibitor of microsomal heme oxygenase. The elevated unconjugated serum bilirubin levels of the neonates receiving this metalloporphyrin rapidly declined to near adult levels by 24-30 h. Control neonates which received an injection of saline exhibited normal physiologic hyperbilirubinemias of from 3-6 mg/dl by 12-24 h as expected. These studies establish the effectiveness of tin-protoporphyrin IX in depressing bilirubin production and preventing physiologic hyperbilirubinemia in simian neonates. Two of six animals receiving the metalloporphyrin exhibited signs of toxicity.

Prevention of neonatal hyperbilirubinemia by tin protoporphyrin IX, a potent competitive inhibitor of heme oxidation.

The effects of various metalloporphyrins on hepatic heme oxygenase (EC 1.14.99.3) activity were examined in order to identify compounds that could inhibit heme degradation to bile pigment and might therefore be utilized to suppress the development of hyperbilirubinemia in the newborn. Among nine metal-protoporphyrin IX chelates (i.e., metal-hemes) studied, Sn-heme, Mn-heme, and Zn-heme substantially diminished heme oxygenase activity in vivo in the rat. These metalloporphyrins act as competitive inhibitory substrates in the heme oxygenase reaction but are not themselves oxidatively degraded. Sn-heme was the most potent enzyme inhibitor (Ki = 0.011 microM) in liver, spleen, kidney, and skin. Sn-heme administered to newborn animals within the first 72 hr after birth blocked the postnatal increase in heme oxygenase activity that occurs in various tissues. Its effect on the enzyme levels was prompt and protracted. Sn-heme administration also entirely prevented the development of hyperbilirubinemia that normally occurs postnatally. The effect of the metalloporphyrin in lowering the increased concentrations of serum bilirubin in neonates was prompt (within 1 day) and persisted throughout the 42 days after birth. No deleterious effects of Sn-heme treatment of the newborn were observed. This demonstrates that a synthetic metalloporphyrin that is a potent competitive inhibitor of heme oxidation can, when administered to the newborn, also prevent the hyperbilirubinemia that normally develops postnatally. The potential clinical implications of these findings are evident, and it is suggested that the pharmacological properties of Sn-heme and related synthetic metalloporphyrins merit further study.