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Annals of Neonatology Journal OPEN ACCESS ISSN: 2636-3596 RESEARCH ARTICLE Assessment of serum levels of vitamin B12 in full term neonates with indirect hyperbilirubinemia Gamal B. Mohamed1, Reem A. Salam1, Rabie H. Mortada1* *Correspondence: Rabie H. Mortada. Department of Pediatrics, Faculty of Medicine, Minia University, Egypt. Email: [email protected] Full list of author information is available at the end of the article DOI: 10.21608/ANJ.2020.69363 Abstract Introduction: Neonatal hyperbilirubinemia is defined as a total serum bilirubin level above 5 mg per dl (85 μmol / L). Jaundice is an important problem in the first week of life. It is a cause of concern for the physician and a source of anxiety for the parents. Objective: The aim of this work was to measure the serum levels of vitamin B12 in neonates with indirect hyperbilirubinemia and to compare them with that of apparently healthy neonates. Subjects and Methods: This study included 80 full term neonates divided into 2 groups: Group I: 40 full term neonates with indirect hyperbilirubinemia (23 females and 17males) aged 3-7 day's admitted to neonatal unit of Minia university hospital during the period from July to December 2017. Group II: 40 apparently healthy full term neonates as controls (20 males and 20 females) of matched age and weight. Results: the vitamin B12 serum levels were significantly lower than in neonates with indirect hyperbilirubinemia than controls (P-value = 0.001*). No statistically significant difference regarding age, sex, mode of delivery, gestational age or weight between patients and controls as were present. Also No statistically significant difference regarding the hemoglobin levels, platelets count, WBCS count or neutrophils count between cases and controls. Conclusion: Full term neonates with indirect hyperbilirubinemia had lower serum levels of vitamin B12 than healthy full term neonates. Key words: Vitamin B12, full term, neonates, hyperbilirubinemia Annals of Neonatology Journal 2020; 2 (1): 20- 26 Mohamed G.B.et al.; 2020. Assessment of serum levels of vitamin B12 in ……………………….. Introduction adenosyl-Cbl, the two enzyme co-factors of Neonatal hyperbilirubinemia is defined as a total methionine synthase and methylmalonyl-CoA serum bilirubin level above 5 mg per dl (85 mutase, respectively. Vitamin B12 deficiency μmol per L). Jaundice is an important problem produces clinical disorders that include mainly in the first week of life. It is a cause of concern megaloblastic anemia, peripheral and central for the physician and a source of anxiety for the neurological manifestations. The clinical parents. Nearly 60% of term newborns become significance of low blood B12 concentrations in visibly jaundiced in the first week of life. In the absence of manifestations of deficiency is a most cases it is benign and no intervention is matter of debate. The biochemical diagnosis of required. Approximately 5-10% of them have the subclinical and clinical deficiency of vitamin clinical significant hyperbilirubinemia B12 has been enriched by several parameters, mandating the use of phototherapy ]1[. including serum methylmalonic acid, Unconjugated hyperbilirubinemia, is the most homocysteine, and holo-transcobalamine, which common form of jaundice encountered by have been evaluated over the past two decades family physicians. Infants without identified risk ]2[ factors rarely have total serum bilirubin levels Vitamin B12 deficiency is known to produce above 12 mg per dl (205 M mol per L). common unconjugated hyperbilirubinaemia due to the risk factors for hyperbilirubinmia include fetal- phenomenon of ineffective erythropoiesis. The maternal blood group incompatibility, resulting hyperbilirubinaemia In the presence of prematurity, and a previously affected sibling, pre-existing conjugation defects such as cephalohematomas, bruisng, and trauma from Gilbert’s syndrome, vitamin B12 deficiency can instrumented delivery may increase the risk for produce gross unconjugated serum bilirubin elevation ]2[ hyperbilirubinaemia ]4[ Vit B12 is essential for DNA synthesis and for Aim of the work cellular energy production. Vitamin B12 The aim of this work was to measure serum deficiency is common, mainly due to limited level of vitamin B12 in neonates with indirect dietary intake of animal foods or malabsorption hyperbilirubinemia and compare them with that of the vitamin ]3[. of apparently healthy neonates of the same age The term "vitamin B12" refers to four and weight. cobalamins (Cbl), including methyl-Cbl and Subjects and Methods Annals of Neonatology Journal 2020; 2 (1): 20- 26 Mohamed G.B.et al.; 2020. Assessment of serum levels of vitamin B12 in ……………………….. The study was approved by the local research 1-Age 3-7 days ethics committee of the faculty of medicine, 2-Gestational age of 37-42 weeks Minia University 3- Birth weight from 2500 gm to 3700 gm This study included 80 full term neonates 4-Good general condition (good moro good divided into 2 groups: Group I included 40 full suckling) term neonates with indirect hyperbilirubinemia 5-Laboratory investigation: (23 females and 17 males) aged 3-7 day's during -Total bilirubin more 5 mg/dl the period from July to December 2017. Group -Direct bilirubin <20% II included 40 apparently healthy full term -CBC: normal Hb level , platelet count and neonates as a control group (20 males and 20 WBCs and no other signs of infection. females) of matched age and weight. - Negative CRP All neonates had informed consents from their Sample procedure: Four ml of venous blood parents and all were subjected to the following: were obtained from each neonate under sterile 1-Complete history taking with stress on the venipuncture and divided as follow: One ml on onset of appearance of jaundice, gestational EDTA containing tube for performing CBC. age, mode of delivery and history suggestive of Three ml were put on plain plastic tube , kept in sepsis (bad general condition, fever, poor the incubator for 20 minutes and centrifuged at `suckling) or suggestive obstructive jaundice 3000r.p.m for 10 minutes to obtain serum which (dark urine and pale stool). was then processed for bilirubin and CRP while 2-Clinical examination was done with stress on the remaining serum stored at -20c in Eppendorf general condition jaundice, pallor, fever, vital cups until processing serum vitamin B12. signs (temperature, respiratory rate, and heart A-CBC assessment: It was done by automated rate), reflexes, weight, and systemic cell counter sysmex KX21N (Japan). examination for organomegaly. B-Serum bilirubin: It was done by automated 3-Laboratory investigations: Complete blood chemical analyzer konelab 201(FILAND). count, C-reactive protein, Total and direct Statistical analysis: bilirubin, Serum vitamin B12 level, Blood group Data were entered and analyzed by SPSS 19. for the neonates and their mothers and Comb's Graphics by excel. Quantitative data presented test as mean and standard deviation, qualitative data Inclusion criteria: presented by frequency distribution. Annals of Neonatology Journal 2020; 2 (1): 20- 26 Mohamed G.B.et al.; 2020. Assessment of serum levels of vitamin B12 in ……………………….. Independent sample t test, chi-square test and factor), hepatic stores are depleted, and Pearson correlation were used. P value of less deficiency occurs ]5[. than 0.05 considered as cutoff for significance. The importance of folate and vitamin B12 for Results: There were no statistical differences healthy neurological development and function regarding age, sex, mode of delivery, gestational is unquestioned. Folate and vitamin B12 are age or weight between patients and controls as required for biological methylation and DNA well as the values of hemoglobin, platelets, synthesis. Vitamin B12 also participates in the WBCS or neutrophils counts (Tables 1 & 2). mitochondrial catabolism of odd-chain fatty There was a significant decrease in serum levels acids and some amino acids. Inborn errors of of vitamin B12 in patients compared to controls their metabolism and severe nutritional (P-value = 0.001*) (Table 3 & Figure 1) while deficiencies cause serious neurological and there was a significant increase in total serum hematological pathology. Poor folate and bilirubin in cases compared to controls as vitamin B12 status is associated with increased expected (Table 3). risk of cognitive impairment, depression, Discussion Alzheimer's disease and stroke among older Vitamin B12 (Cobalamin) is a water-soluble adults and increased risk of neural tube defects vitamin that is derived from animal products among children born to mothers with low folate meat, dairy, and eggs. Intrinsic factor is a status]6[ glycoprotein that is produced by parietal cells in NNH is a frequently encountered problem. the stomach and necessary for the absorption of Although up to 60% of term newborns have B12 in the terminal ileum such as red. Once clinical jaundice in the first week of life, few absorbed, B12 is used as a cofactor for enzymes have significant underlying disease. Physiologic that are involved in the synthesis of DNA, fatty jaundice in healthy term newborns follows a acids, and myelin. As a result, a B12 deficiency typical pattern. All etiologies of jaundice can lead to hematologic and neurologic beyond physiologic and breastfeeding or breast symptoms. B12 is stored in excess in the liver; milk jaundice are considered pathologic. however, in cases in which B12 cannot be Pathologic jaundice can result from ABO and absorbed for a prolonged period (e.g., dietary Rh