|Year : 2019 | Volume
| Issue : 4 | Page : 222-226
Detection of serum levels of Vitamin C, D, and E in neonatal jaundice
Mohamed Shawky Elfarargy1, Dina Adam Ali2, Ghada Mohamed Al-Ashmawy3, Saad Ahmed Mohamed4
1 Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta, El-Gharbia, Egypt
2 Departments of Clinical Pathology, Tanta University, Tanta, El-Gharbia, Egypt
3 Departments of Biochemistry, Tanta University, Tanta, El-Gharbia, Egypt
4 Department of Nutritional Pediatrics, Al-Azhar University, New Damietta, Egypt
|Date of Submission||03-Mar-2019|
|Date of Decision||01-Sep-2019|
|Date of Acceptance||08-Sep-2019|
|Date of Web Publication||04-Oct-2019|
Dr. Mohamed Shawky Elfarargy
Assistant Professor of Pediatrics and Neonatology, Faculty of Medicine, Tanta University, Tanta, El-Gharbia
Source of Support: None, Conflict of Interest: None
Background: Neonatal jaundice is a large problem in the neonates causing many complications in the newborn that need further studies on this common problem. Patients and Methods: This study is considered a case–control study which was done in the neonatal unit of Tanta University Hospital from May 2016 to March 2018. It was done on 100 full-term neonates. A study group which includes 50 neonates admitted in the neonatal unit as they are diagnosed with neonatal jaundice with their bilirubin levels ranging from 15 to 19 mg/dl and 50 healthy outpatient neonates act as a control group. We detect the serum levels of Vitamin C, D, and E in both groups. Results: Serum levels of Vitamin C, D, and E were significantly lower in the study group which include the cases of neonatal jaundice if compared their levels in the control healthy group with negative statistically significant correlation which is present between the serum levels of the bilirubin and the serum levels of Vitamin C, D, and E in the study group. Conclusion: The results of this study revealed that low serum levels of Vitamins C, D, and E are present in neonatal jaundice group indicating that neonatal jaundice is accompanied by decrease the serum levels of these vitamins attracting the attention of the researchers to study the effect of these vitamin supplementations as an adjuvant therapy in neonatal jaundice.
Keywords: Bilirubin, neonatal jaundice, Vitamin C, Vitamin D, Vitamin E
|How to cite this article:|
Elfarargy MS, Ali DA, Al-Ashmawy GM, Mohamed SA. Detection of serum levels of Vitamin C, D, and E in neonatal jaundice. J Clin Neonatol 2019;8:222-6
|How to cite this URL:|
Elfarargy MS, Ali DA, Al-Ashmawy GM, Mohamed SA. Detection of serum levels of Vitamin C, D, and E in neonatal jaundice. J Clin Neonatol [serial online] 2019 [cited 2020 Jan 24];8:222-6. Available from: http://www.jcnonweb.com/text.asp?2019/8/4/222/268585
| Introduction|| |
Neonatal jaundice is a considered as the yellow coloration of the skin, mucus membrane, and sclera due to elevated levels of indirect bilirubin above the normal values, neonatal jaundice is still one of the common famous problems in the neonates. Neonatal jaundice or indirect hyperbilirubinemia may cause many serious problems like kernicterus which is also called bilirubin encephalopathy and may lead to permanent sequaele and even death. Neonatal jaundice or hyperbilirubinemia may be caused by increased hemolysis which leads to increased bilirubin formation or decline in conjugation of bilirubin in the hepatocytes. Neonatal jaundice may need follow-up, phototherapy or may need exchange blood transfusion. Vitamin D is considered one of the vitamins which are fat-soluble which is found in many foods and needs the functions of the kidney and the role of hepatocytes for its activation. It has various function including helping in absorption of calcium with teeth and bone formation, improving muscle function and has an important function in immune system. Furthermore, Vitamin D activation happens through 25-hydroxylation in the hepatocytes then followed by 1-hydroxylation in the kidney. The liver is not only tangled in Vitamin D formation but also has a key function in metabolizing indirect bilirubin to direct bilirubin. The metabolisms of Vitamin D and bilirubin occur in two distinct pathways, but they may influence each other during biosynthesis stage in the liver. The phase of 25-hydroxylation is considered a cornerstone phases of the formation of Vitamin D, which is present in the liver, in addition to bilirubin conjugation. Vitamin D had a protective function to the liver through anti-inflammatory effect, and the liver plays an important role in detoxification of the bilirubin and changing it from unconjugated or indirect bilirubin which can pass the blood–brain barrier of the neonates causing kernicterus to conjugated or direct bilirubin which cannot pass the blood–brain barrier of the neonates and hence, the liver cause decrease in indirect hyperbilirubinemia and hence, Vitamin D should have a role in helping the liver to decrease the neonatal jaundice., Some researchers studied the levels of Vitamin D in the neonates who diagnosed with neonatal jaundice, but still the results need more studies on big number of neonates.,
Hemolysis of the red blood cells (RBCs) in the neonates which had short life span which is 80 days will lead to neonatal jaundice., Neonatal RBCs are liable to damage by oxidative substances which is due to decreased the system which acts as antioxidant which protects the RBCs from oxidative stress., Vitamin C is considered a water-soluble vitamin which is also called ascorbic acid. Vitamin C helps produce collagen which is considered as a protein which is needed for formation of healthy teeth, skeleton, gums, cartilage, skin, and blood vessels, it is found mainly in some fruits and many vegetables. Vitamin E is considered one of the vitamins that are water-soluble, it possesses an important function of the neurological and immune process and also it acts as antioxidant which protects the tissues against the hazardous effect which is produced by free radicals, it is present in vegetable oils, nuts, and seed. Nonenzymatic antioxidants such as Vitamin C and E represent the body defense mechanism against oxidative damage so protecting the neonatal RBCs from damage by oxidative substances and prevent the hemolysis of the neonatal RBCs which will lead to neonatal jaundice.,, Some researches detected reduction in Vitamin C and others detected reduction in Vitamin E in neonatal jaundice as these antioxidant vitamins are consumed to counteract the oxidative damage of the RBCs of the neonates which occur in neonatal hyperbilirubinemia.,
Decreased the levels of Vitamin C and E which act as antioxidant to protect the membranes of RBCs against oxidative injury are reported in some studies, but still that point needs more researches on many number of neonates., The aim of this study was to detect the serum levels of Vitamin C, D, and E in neonates suffering from neonatal jaundice and compare their serum levels with healthy normal neonates.
| Patients and Methods|| |
A case–control study which includes 50 jaundiced full-term neonates as a study group and 50 neonates who are healthy and also full-term neonates as a control group. The study was conducted in Tanta university hospital from May 2016 to March 2018. All applicants were requested from the parents of the neonates to sign an informed form of consent before inclusion in the study. This study had been accepted by the Committee of Ethics of the Faculty of Medicine and Pharmacy, Tanta University.
History and investigations to the neonates and also to their mothers were obtained as follows: history of Vitamin C, D, or E administration during pregnancy, history of the mothers' disease, the 25-hydroxycholecalciferol level of the neonates, the Ca 2+ (calcium) and Mg 2+ (magnesium) levels.
Inclusion criteria included full-term neonates, bilirubin level from 15 to 19 mg/dl on the 3rd day of life in the study group, neonates who required phototherapy according to the American Academy of Pediatrics, mothers of studied neonates had normal serum Vitamin C, D, and E levels.
Exclusion criteria included preterm neonates, neonates who need exchange blood transfusion, direct hyperbilirubinemia, congenital anomalies, hypothyroidism and sepsis, neonates who had Vitamin C, D, or E supplementation during the period of the study, mothers with liver, kidney disease, diabetic mothers or mothers who take medication such as anticonvulsants and Vitamin C, D, or E supplementation.
A venous blood sample (4 ml) was withdrawn from each neonate using a sterile BD vacutainer butterfly needle just after admission to incubator before exposure to phototherapy where it was processed immediately after withdrawal. Each blood sample was divided into two portions (2 ml each). The first portion was collected in a BD vacutainer serum separator tube, and serum samples were separated after centrifugation and stored at −20°C until 25-hydroxy Vitamin D (calcidiol) and total bilirubin levels were assessed. The second portion was delivered in a tube-containing heparin; plasma was separated after centrifugation and stored at −20°C until analysis of other biomarkers (Vitamin C, Vitamin E).
The serum total bilirubin was detected using the colorimetric method. The serum 25-hydroxy Vitamin D values were evaluated using enzyme-linked of the immunosorbent assay (ELISA) kits, according to the instructions of the manufactured (R and D Systems Inc ®, Catalog number RDKAP1971, USA), using Awareness Technology ® (USA) ELISA reader. 25-hydroxy Vitamin D concentration was expressed as ng/ml.
Vitamin C and Vitamin E were determined in heparinized plasma samples using ELISA kits obtained from SunRed Biological Technology ® (China) according to the manufacturers' instructions. Both vitamin concentrations were expressed as μmol/L.
Data are expressed as a mean ± standard deviation, range. The t-test was done for group comparisons of normally distributed variables. The computer SPSS (SPSS 21, IBM, Armonk, NY, United States of America) program had been done for every statistical calculation, version 21 were used in the statistical analysis, USA. P < 0.05 was considered as statistically significant.
| Results|| |
[Table 1] shows the different characteristics between studied groups which revealed that no statistical difference between both groups as regards the weight, gestational age, mode of delivery, and the sex.
[Table 2] reveals that difference which is considered statistically significant (P = 0.001) between the study neonate group (n = 50) and the control neonate group (n = 50) as regards bilirubin serum levels and Vitamin C, D, and E serum levels.
|Table 2: A comparison between the serum levels of bilirubin and Vitamins C, D, E between both groups on the third day of life (n=50)|
Click here to view
[Table 3] shows that there was a statistically negative significant correlation between bilirubin serum levels and the serum levels of Vitamin C, D, and E.
|Table 3: Correlation between bilirubin and serum levels of Vitamin C, D, and E in the study group|
Click here to view
| Discussion|| |
Neonatal jaundice which is due to an increase in bilirubin level had various methods in the prevention and treatment, which include phototherapy, phenobarbitone administration exchange blood transfusion, and intravenous immunoglobulin administration. The study of serum levels of vitamins such as Vitamin C, D, and E may open the way for finding another adjuvant treatment for this problem which is present all worldwide.
This study revealed that there was decline in levels of Vitamin D in the serum in the study group with neonatal jaundice on the 3rd day of life in comparison to the control healthy neonates who do not develop neonatal jaundice until the 3rd day of life.
This study found that there were significant decline in the levels of Vitamin C, D, and E in the serum in the study group which consists of 50 full-term jaundiced neonates where their bilirubin levels ranging from 15 to 19 mg/dl in comparison of the control group which consists of 50 full-term healthy neonates without jaundice on the 3rd day of life ranging their bilirubin levels from 2.1 to 4.4 (P < 0.001*) with statistically negative significant correlation between the serum levels of bilirubin serum levels and Vitamin C, D, and E serum levels.
The study found to decline in the Vitamin D levels in the serum in neonates which had jaundice in the study group which attract our attention about the value of Vitamin D in neonatal jaundice, but there are some studies which disagree with this study and stated that it was no relationship between the blood levels of Vitamin D and the event of cases of neonatal hyperbilirubinemia making more researches in this topic will be needed.
In agreement with this study, there are some researches and studies which turned out that the adding supplementation of Vitamin D to the pregnant mothers were associated with declined the levels of neonatal hyperbilirubinemia which may tell the researchers that Vitamin D is vital in declining the levels of bilirubin in neonates with jaundice and may tell us that the neonates with jaundice had low Vitamin D levels and to recommend that mothers to take Vitamin D to decline the levels of bilirubin in their neonates.
In disagreement with this study, another study done to correlate between blood levels of Vitamin D and the event of jaundice in neonates that found that it was no correlation, if there was association between the blood levels of Vitamin D in neonates and the event of jaundice in neonates, but the study stated that the jaundiced neonates are not accompanied by decline in the levels of Vitamin D.
In agreement with this study, there was a study which proved that there was decreased in Vitamin D values in neonatal jaundice if compared with the control group who did not develop neonatal hyperbilirubinemia which showed statistically significant difference in the Vitamin D values and the healthy neonates which no neonatal jaundice.,,
The RBCs of the newborn are liable to hemolysis which is due to peroxide rupture of the membrane of the neonatal RBCs due to persistent exposure to high levels of oxygen and other oxidant substances.
Vitamin C and Vitamin E are considered as antioxidants that protect the cell wall of the neonatal RBCs from various oxidants that cause rupture of the RBCs of the neonates and thus produce hyperbilirubinemia.
In this study, we detect the serum levels of Vitamin C and E in neonates on the 3rd day of life either in the study group who represent the neonates which had neonatal jaundice with raised bilirubin value from 15 to 19 mg/dl which needed phototherapy only. The results were revealed that there was decline in the Vitamin C and E serum levels in the study group which had neonatal jaundice with increase in their bilirubin levels in comparison with control healthy group with absent neonatal jaundice and decreased serum bilirubin value with the same criteria.
In agreement with this study, there are studies that stated that there declined levels of Vitamin C and E in the neonates who suffered from neonatal jaundice and increased serum levels of bilirubin if they are compared with nonjaundiced neonates with low levels of serum bilirubin.,
Some researchers concluded that the serum levels of maternal Vitamin A affected the morbidity and mortality of the neonates delivered by theses mothers, but they did not state that there was no significant role of Vitamin C and E in neonatal jaundice and increased the level of serum bilirubin in the neonates.
In agreement with this study, there was decrease in levels of antioxidant vitamins which include Vitamin A, C, and E in neonates which suffered from neonatal jaundice with increased bilirubin level, but in comparison with our study which examines full-term neonates this study stated that the decreased levels of Vitamin A, C, D were associated with hyperbilirubinemia in neonates.
In agreement with this study which showed decrease in Vitamin C levels in neonatal jaundice, there was a study which also stated that the neonatal jaundice is accompanied by oxidative stress which leads to decline in the levels of Vitamin C and other antioxidants which include Vitamin E and the declined serum levels of antioxidants lead to rupture of the RBCs membrane with subsequent neonatal hyperbilirubinemia.
| Conclusion|| |
The results of this study revealed that low serum levels of Vitamins C, D, and E are present in neonatal jaundice group indicating that neonatal jaundice is accompanied by decrease the serum levels of these vitamins attracting the attention of the researchers to study the effect of these vitamin supplementations as an adjuvant treatment in neonatal jaundice.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Leung TS, Outlaw F, MacDonald LW, Meek J. Jaundice eye color index (JECI): Quantifying the yellowness of the sclera in jaundiced neonates with digital photography. Biomed Opt Express 2019;10:1250-6.
Bahr TM, Christensen RD, Agarwal AM, George TI, Bhutani VK. The neonatal acute bilirubin encephalopathy registry (NABER): Background, aims, and protocol. Neonatology 2019;115:242-6.
Bhutani VK, Maisels MJ, Schutzman DL, Castillo Cuadrado ME, Aby JL, Bogen DL, et al.
Identification of risk for neonatal haemolysis. Acta Paediatr 2018;107:1350-6.
Fein EH, Friedlander S, Lu Y, Pak Y, Sakai-Bizmark R, Smith LM, et al.
Phototherapy for neonatal unconjugated hyperbilirubinemia: Examining outcomes by level of care. Hosp Pediatr 2019;9:115-20.
Horan MP, Williams K, Hughes D. The role of Vitamin D in pediatric orthopedics. Orthop Clin North Am 2019;50:181-91.
Tayel SI, Soliman SE, Elsayed HM. Vitamin D deficiency and Vitamin D receptor variants in mothers and their neonates are risk factors for neonatal sepsis. Steroids 2018;134:37-42.
Kassai MS, Cafeo FR, Affonso-Kaufman FA, Suano-Souza FI, Sarni RO. Vitamin D plasma concentrations in pregnant women and their preterm newborns. BMC Pregnancy Childbirth 2018;18:412.
Ariyawatkul K, Lersbuasin P. Prevalence of Vitamin D deficiency in cord blood of newborns and the association with maternal Vitamin D status. Eur J Pediatr 2018;177:1541-5.
Aletayeb SM, Dehdashtiyan M, Aminzadeh M, Malekyan A, Jafrasteh S. Comparison between maternal and neonatal serum Vitamin D levels in term jaundiced and nonjaundiced cases. J Chin Med Assoc 2016;79:614-7.
Elsary AY, Elgameel AA, Mohammed WS, Zaki OM, Taha SA. Neonatal hypocalcemia and its relation to Vitamin D and calcium supplementation. Saudi Med J 2018;39:247-53.
Pearson HA. Life-span of the fetal red blood cell. J Pediatr 1967;70:166-71.
Lorenz L, Peter A, Arand J, Springer F, Poets CF, Franz AR, et al.
Reticulocyte haemoglobin content declines more markedly in preterm than in term infants in the first days after birth. Neonatology 2017;112:246-50.
Ferencz Á, Orvos H, Hermesz E. Major differences in the levels of redox status and antioxidant defence markers in the erythrocytes of pre – And full-term neonates with intrauterine growth restriction. Reprod Toxicol 2015;53:10-4.
Dugmonits KN, Ferencz Á, Zahorán S, Lázár R, Talapka P, Orvos H, et al.
Elevated levels of macromolecular damage are correlated with increased nitric oxide synthase expression in erythrocytes isolated from twin neonates. Br J Haematol 2016;174:932-41.
Darlow BA, Buss H, McGill F, Fletcher L, Graham P, Winterbourn CC, et al.
Vitamin C supplementation in very preterm infants: A randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2005;90:F117-22.
Pacifici GM. Effects of Vitamin E in neonates and young infants. Int J Pediatr 2016;4:1745-57.
Traber MG, Stevens JF. Vitamins C and E: Beneficial effects from a mechanistic perspective. Free Radic Biol Med 2011;51:1000-13.
Turgut M, Başaran O, Cekmen M, Karataş F, Kurt A, Aygün AD, et al.
Oxidant and antioxidant levels in preterm newborns with idiopathic hyperbilirubinaemia. J Paediatr Child Health 2004;40:633-7.
Bracci R, Buonocore G, Talluri B, Berni S. Neonatal hyperbilirubinemia. Evidence for a role of the erythrocyte enzyme activities involved in the detoxification of oxygen radicals. Acta Paediatr Scand 1988;77:349-56.
Mirzarahimi M, Ahadi A, Bohlooli S, Namakikhalajan E, Barak M. Antioxidant levels in cord blood of term neonates and its association with birth weight. Iran J Child Neurol 2016;10:31-4.
Lucock M, Jones P, Martin C, Yates Z, Veysey M, Furst J, et al.
Photobiology of vitamins. Nutr Rev 2018;76:512-25.
Szasz G. A kinetic photometric method for serum gamma-glutamyl transpeptidase. Clin Chem 1969;15:124-36.
Watchko JF. Identification of neonates at risk for hazardous hyperbilirubinemia: Emerging clinical insights. Pediatr Clin North Am 2009;56:671-87.
Jahanjoo F, Farshbaf-Khalili A, Shakouri SK, Dolatkhah N. Maternal and neonatal metabolic outcomes of Vitamin D supplementation in gestational diabetes mellitus: A systematic review and meta-analysis. Ann Nutr Metab 2018;73:145-59.
Mehrpisheh S, Memarian A, Mahyar A, Valiahdi NS. Correlation between serum Vitamin D level and neonatal indirect hyperbilirubinemia. BMC Pediatr 2018;18:178.
Ayyappan S, Philip S, Bharathy N, Ramesh V, Kumar CN, Swathi S, et al.
Antioxidant status in neonatal jaundice before and after phototherapy. J Pharm Bioallied Sci 2015;7:S16-21.
Mutlu M, Çayir A, Çayir Y, Özkan B, Aslan Y. Vitamin D and hyperbilirubinaemia in neonates. HK J Paediatr (New Ser) 2013;18:77-81.
Wang YZ, Ren WH, Liao WQ, Zhang GY. Concentrations of antioxidant vitamins in maternal and cord serum and their effect on birth outcomes. J Nutr Sci Vitaminol (Tokyo) 2009;55:1-8.
[Table 1], [Table 2], [Table 3]