新生儿高胆红素血症病因研究进展
Research Progress in Etiology of Neonatal Hyperbilirubinemia
DOI: 10.12677/ACM.2022.1281161, PDF,   
作者: 召 拉, 刘春枝*, 白 璐, 许玉红:内蒙古医科大学附属医院新生儿科,内蒙古 呼和浩特
关键词: 新生儿高胆红素血症病因溶血遗传种族及地域Neonatal Hyperbilirubinemia Pathogeny Hemolysis Heredity Race and Region
摘要: 新生儿高胆红素血症是新生儿出生后需住院治疗的最常见病因,也是新生儿时期再次入院的主要原因,其是由血清胆红素的产生和消除之间的不平衡引起的,主要是红细胞分解的结果。新生儿高胆红素血症为多因素多基因参与的疾病,包括孕母妊娠期并发症、早产、新生儿感染、基因、种族地域及不明原因等。新生儿高胆红素血症通过光疗等积极有效处理得到缓解,但仍可见病情进展造成不可逆的严重后果,如重度高胆红素血症引起胆红素脑病,即未结合胆红素穿过血脑屏障,可留下脑瘫、智力发育受损和神经性耳聋等不可逆神经系统损伤,甚至危机患儿生命。因此,明确新生儿高胆红素血症的常见病因,为早期筛查、积极预防及及时诊断提供有效依据,降低其发生率。
Abstract: Neonatal hyperbilirubinemia is the most common cause of hospitalization after birth, and also the main cause of readmission during the neonatal period. It is caused by the imbalance between the production and elimination of serum bilirubin, which is mainly the result of erythrocyte decompo-sition. Neonatal hyperbilirubinemia is a disease involving multiple factors and genes, including maternal complications during pregnancy, premature delivery, neonatal infection, genes, race, re-gion and unknown causes. Neonatal hyperbilirubinemia has been relieved through active and effec-tive treatment such as phototherapy, but it can still be seen that the progress of the disease has caused irreversible serious consequences. For example, severe hyperbilirubinemia causes bilirubin encephalopathy, that is, unconjugated bilirubin crosses the blood-brain barrier, which can leave ir-reversible nervous system damage such as cerebral palsy, impaired intellectual development and neurogenic deafness, and even endanger the lives of children. Therefore, we need to identify the common causes of neonatal hyperbilirubinemia, provide effective basis for early screening, active prevention and timely diagnosis, and reduce its incidence.
文章引用:召拉, 刘春枝, 白璐, 许玉红. 新生儿高胆红素血症病因研究进展[J]. 临床医学进展, 2022, 12(8): 8063-8070. https://doi.org/10.12677/ACM.2022.1281161

参考文献

[1] Olusanya, B.O., Ogunlesi, T.A., Kumar, P., et al. (2015) Management of Late-Preterm and Term Infants with Hyperbili-rubinaemia in Resource-Constrained Settings. BMC Pediatrics, 15, Article No. 39. [Google Scholar] [CrossRef] [PubMed]
[2] Hossain, M., Begum, M., Ahmed, S. and Absar, M.N. (2015) Causes, Management and Immediate Complications of Management of Neonatal Jaundice—A Hospital-Based Study. Journal of Enam Medical College, 5, 104-109. [Google Scholar] [CrossRef
[3] Dani, C., Poggi, C. and Pratesi, S. (2018) Bilirubin and Oxidative Stress in Term and Preterm Infants. Free Radical Research, 53, 2-7. [Google Scholar] [CrossRef] [PubMed]
[4] Creeden, J.F., Gordon, D.M., Stec, D.E., et al. (2020) Bili-rubin as a Metabolic Hormone: The Physiological Relevance of Low Levels. AJP Endocrinology and Metabolism, 320, E191-E207. [Google Scholar] [CrossRef] [PubMed]
[5] Fujiwara, R., Haag, M., Schaeffeler, E., et al. (2018) Systemic Regulation of Bilirubin Homeostasis: Potential Benefits of Hyperbilirubinemia. Hepatology, 67, 1609-1619. [Google Scholar] [CrossRef] [PubMed]
[6] Bhutani, V.K. and Wong, R. (2015) Bilirubin-Induced Neurologic Dys-function (BIND). Seminars in Fetal & Neonatal Medicine, 20, 1. [Google Scholar] [CrossRef] [PubMed]
[7] Olusanya, B.O., Teeple, S. and Kassebaum, N.J. (2018) The Con-tribution of Neonatal Jaundice to Global Child Mortality: Findings from the GBD 2016 Study. Pediatrics, 141, Article ID: e20171471. [Google Scholar] [CrossRef] [PubMed]
[8] Alkén, J., Håkansson, S., Ekéus, C., et al. (2019) Rates of Extreme Neonatal Hyperbilirubinemia and Kernicterus in Children and Adherence to National Guidelines for Screening, Diagnosis, and Treatment in Sweden. JAMA Network Open, 2, Article ID: e190858. [Google Scholar] [CrossRef] [PubMed]
[9] Lozada, L.E., Nylund, C.M., Gorman, G.H., et al. (2015) Association of Autism Spectrum Disorders with Neonatal Hyperbilirubinemia. Global Pediatric Health, 2, Article ID: 2333794X15596518. [Google Scholar] [CrossRef
[10] Kuzniewicz, M.W., Hamid, N., Walsh, E.M., et al. (2018) Hy-perbilirubinemia, Phototherapy, and Childhood Asthma. Pediatrics, 142, Article ID: e20180662. [Google Scholar] [CrossRef] [PubMed]
[11] Wei, C.C., Chang, C.H., Lin, C.L., et al. (2015) Neonatal Jaundice and Increased Risk of Attention-Deficit Hyperactivity Disorder: A Population-Based Cohort Study. Journal of Child Psychology & Psychiatry & Allied Disciplines, 56, 460-467. [Google Scholar] [CrossRef] [PubMed]
[12] Maimburg, R.D., Olsen, J. and Sun, Y. (2016) Neonatal Hyperbilirubinemia and the Risk of Febrile Seizures and Childhood Epilep-sy. Epilepsy Research, 124, 67-72. [Google Scholar] [CrossRef] [PubMed]
[13] 黄家虎, 孙建华. 新生儿高胆红素血症病因的研究进展[J]. 医学综述, 2021, 27(4): 680-684.
[14] Nam, G.S., Kwak, S.H., Bae, S.H., et al. (2019) Hyperbilirubinemia and Follow-up Auditory Brainstem Responses in Preterm Infants. Clinical and Experimental Otorhinolaryngology, 12, 163-168. [Google Scholar] [CrossRef] [PubMed]
[15] Campbell Wagemann, S. and Mena Nannig, P. (2019) Hiperbilirru-binemia severa en Recién Nacidos, factores de riesgo y secuelas neurológicas [Severe Hyperbilirubinemia in Newborns, Risk Factors and Neurological Outcomes]. Revista Chilena de Pediatría, 90, 267-274. (Spanish) [Google Scholar] [CrossRef] [PubMed]
[16] 段姗姗 . 新生儿高非结合胆红素血症的发病原因分析[J]. 山西卫生健康职业学院学报, 2019, 29(5): 111-113
[17] Pillai, A., Pandita, A., Osiovich, H., et al. (2020) Pathogenesis and Management of Indirect Hyperbilirubinemia in Preterm Neonates Less than 35 Weeks: Moving Toward a Standard-ized Approach. NeoReviews, 21, e298-e307. [Google Scholar] [CrossRef] [PubMed]
[18] Aynalem, S., Abayneh, M., Metaferia, G., et al. (2020) Hyperbiliru-binemia in Preterm Infants Admitted to Neonatal Intensive Care Units in Ethiopia. Global Pediatric Health, 7, Article ID: 2333794X20985809. [Google Scholar] [CrossRef
[19] 姚丽萍, 田佳. 新生儿高胆红素血症病因构成随时间变迁分析[J]. 中国妇幼保健, 2016, 31(21): 4456-4459.
[20] Mohammad-Beigi, A., Tabatabaee, S.H.R., Yazdani, M., et al. (2007) Gestational Diabetes Related Unpleasant Outcomes of Pregnancy [Persian]. Feyz Journals of Kashan University of Medical Sciences, 11, 1-6.
[21] Maamouri, G., Boskabadi, H.M., Af Inejad, S., et al. (2014) Efficacy of Oral Zinc Sulfate Intake in Prevention of Neonatal Jaundice. Iranian Journal of Neonatology, 4, 11-16.
[22] Yu, Y., Choi, J., Lee, M.H., et al. (2022) Maternal Disease Factors Associated with Neonatal Jaundice: A Case-Control Study. BMC Preg-nancy and Childbirth, 22, Article No. 247. [Google Scholar] [CrossRef] [PubMed]
[23] Akorsu, E.E., Ac-quaye, J.K., Benneh, A.A., et al. (2019) Fetomaternal Hemorrhage among Pregnant Women in Accra, Ghana. Interna-tional Journal of Gynecology & Obstetrics, 146, 333-338. [Google Scholar] [CrossRef] [PubMed]
[24] Ansong-Assoku, B., Shah, S.D., Adnan, M., et al. (2022) Neonatal Jaundice. 2022 Feb 19. In: StatPearls, StatPearls Publishing, Treasure Island.
[25] Bel Hadj, I., Boukhris, R., Khalsi, F., et al. (2019) ABO Hemolytic Disease of Newborn: Does newborn’s Blood Group a Risk Factor? La Tunisie médicale, 97, 455-460.
[26] 姚润, 杨涓, 李宁. 不同血型系统胎儿或新生儿溶血病的特点[J]. 临床血液学杂志, 2021, 34(12): 890-893.
[27] 邓虹艳, 赵广平, 张梦, 等. 不同因素对O型血孕妇血清IgG抗A(B)抗体效价及新生儿溶血病发生率的影响[J]. 河北医药, 2022, 44(6): 916-918+922.
[28] Metcalf, R.A., Khan, J., Andrews, J., et al. (2019) Severe ABO Hemolytic Disease of the Newborn Requiring Exchange Transfusion. Journal of Pediatric Hematology, 41, 632-634. [Google Scholar] [CrossRef
[29] 陈阳. RhD阴性孕妇的产前同种免疫分析及围产期新生儿溶血病的监测和预防[J]. 临床输血与检验, 2022, 24(1): 42-45.
[30] Costumbrado, J., Mansour, T. and Ghassemzadeh, S. (2022) Rh Incompatibility. 2021 Dec 14. In: StatPearls, StatPearls Publishing.
[31] 金方思, 陈通, 黄颖, 等. “二孩”母婴结局与新生儿Rh溶血病的关联[J]. 临床血液学杂志, 2021, 34(6): 428-431.
[32] Sarwar, A. and Sridhar, D.C. (2020) Rh-Hemolytic Disease. In: StatPearls, StatPearls Publishing, Treasure Island.
[33] Okulu, E., Erdeve, Ö., Tuncer, O., et al. (2021) Exchange Transfusion for Neonatal Hyperbilirubinemia: A Multicenter, Prospective Study of Turkish Neonatal Society. Turkish Archives of Pediatrics, 56, 121-126. [Google Scholar] [CrossRef] [PubMed]
[34] 张榕, 李正秋, 张帆, 等. 血浆置换治疗换血失败的新生儿Rh溶血病疗效分析[J]. 中华新生儿科杂志, 2020, 35(5): 364-367.
[35] Zahed Pasha, Y., Alizadeh-Tabari, S., Zahed Pasha, E., et al. (2020) Etiology and Therapeutic Management of Neonatal Jaundice in Iran: A Systematic Review and Meta-Analysis. World Journal of Pediatrics, 16, 480-493. [Google Scholar] [CrossRef] [PubMed]
[36] 叶宝妮, 刘俐, 李小权, 等. 消退延迟的新生儿高胆红素血症病因分析及转归[J]. 中国妇幼健康研究, 2021, 32(5): 735-739.
[37] 游森水, 曾靖平. 新生儿高胆红素血症病因分析及临床治疗效果评价[J]. 中外医疗, 2020, 39(27): 37-39.
[38] Mei, H., Dong, X., Wu, B., et al. (2021) Clini-cal and Genetic Etiologies of Neonatal Unconjugated Hyperbilirubinemia in the China Neonatal Genomes Project. Pediat-rics, 243, 53-60.e9. [Google Scholar] [CrossRef] [PubMed]
[39] 何翠红, 屈艺. 新生儿高胆红素血症与基因多态性研究进展[J]. 中国当代儿科杂志, 2020, 22(3): 280-284.
[40] Luzzatto, L., Ally, M. and Notaro, R. (2020) Glucose-6-Phosphate Dehydrogenase Deficiency. Blood, 136, 1225-1240. [Google Scholar] [CrossRef] [PubMed]
[41] Howes, R.E., Battle, K.E., Satyagraha, A.W., et al. (2013) G6PD Deficiency: Global Distribution, Genetic Variants and Primaquine Therapy. Advances in Parasitology, 81, 133-201. [Google Scholar] [CrossRef
[42] Koromina, M., Pandi, M.T., van der Spek, P.J., et al. (2021) The Ethnogeographic Variability of Genetic Factors Underlying G6PD Deficiency. Pharmacological Research, 173, Article ID: 105904. [Google Scholar] [CrossRef] [PubMed]
[43] Pan, J., Zhuang, D., Yu, Q., et al. (2021) Molecular Genotyping of G6PD Mutations for Neonates in Ningbo Area. Journal of Clinical Laboratory Analysis, 35, Article ID: e24104. [Google Scholar] [CrossRef] [PubMed]
[44] Wu, C.X., Shan, K.R., He, Y., et al. (2007) Detection of Glu-cose-6-Phosphate Dehydrogenase Gene Mutations of Tujia Ethnic in Jiangkou, Guizhou. Chinese Journal of Endemiol-ogy, 26, 415-417. (In Chinese)
[45] He, Y., Zhang, Y., Chen, X., et al. (2020) Glucose-6-Phosphate Dehydrogenase Deficiency in the Han Chinese Population: Molecular Characterization and Genotype-Phenotype Association throughout an Activity Distribution. Scientific Reports, 10, Article No. 17106. [Google Scholar] [CrossRef] [PubMed]
[46] Liu, D., Yu, Q., Ning, Q., et al. (2021) The Relationship be-tween UGT1A1 Gene & Various Diseases and Prevention Strategies. Drug Metabolism Reviews, 54, 1-21. [Google Scholar] [CrossRef] [PubMed]
[47] Mohammed, A.E., Behiry, E.G., El-Sadek, A.E., et al. (2016) Case-Controlled Study on Indirect Hyperbilirubinemia in Exclusively Breast Fed Neonates and Mutations of the Bilirubin Uridine Diphosphate-Glucuronyl Transferase Gene 1A1. Annals of Medicine and Surgery, 13, 6-12. [Google Scholar] [CrossRef] [PubMed]
[48] Sato, H., Uchida, T., Toyota, K., et al. (2013) Association of Breast-Fed Neonatal Hyperbilirubinemia with UGT1A1 Polymorphisms: 211G>A (G71R) Mutation Becomes a Risk Factor under Inadequate Feeding. Journal of Human Genetics, 58, 7-10. [Google Scholar] [CrossRef] [PubMed]
[49] Yang, H., Lin, F., Chen, Z.K., et al. (2021) UGT1A1 Mutation Associa-tion with Increased Bilirubin Levels and Severity of Unconjugated Hyperbilirubinemia in ABO Incompatible Newborns of China. BMC Pediatrics, 21, Article No. 259. [Google Scholar] [CrossRef] [PubMed]
[50] Wang, J., Yin, J., Xue, M., et al. (2020) Roles of UGT1A1 Gly71Arg and TATA Promoter Polymorphisms in Neonatal Hyperbiliru-binemia: A Meta-Analysis. Gene, 736, Article ID: 144409. [Google Scholar] [CrossRef] [PubMed]
[51] 武华红, 张亚钦, 宗心南, 等. 中国九市城郊2岁以下婴幼儿母乳喂养现状及1985年至2015年的变化趋势[J]. 中华围产医学杂志, 2019(7): 445-450.
[52] Weng, Y.H., Cheng, S.W., Yang, C.Y., et al. (2018) Risk Assessment of Pro-longed Jaundice in Infants at One Month of Age: A Prospective Cohort Study. Scientific Reports, 8, Article No. 14824. [Google Scholar] [CrossRef] [PubMed]
[53] 丁国芳. 母乳喂养和母乳喂养性黄疸[J]. 中华围产医学杂志, 2016, 19(11): 804-807.
[54] Duan, M., Han, Z.H., Huang, T., et al. (2021) Characterization of Gut Microbiota and Short-Chain Fatty Acid in Breastfed Infants with or without Breast Milk Jaundice. Letters in Applied Microbiology, 72, 60-67. [Google Scholar] [CrossRef] [PubMed]
[55] 杨丽菲, 李菁, 胡瑞, 等. 人乳脂肪酸组分与新生儿母乳性黄疸的相关性分析[J]. 中国当代儿科杂志, 2020, 22(12): 1256-1260.
[56] Prameela, K.K. (2019) Breastfeeding during Breast Milk Jaundice—A Pathophysiological Perspective. Medical Journal of Malaysia, 74, 527-533.
[57] Wickremasinghe, A.C., Kuzniewicz, M.W. and Newman, T.B. (2013) Black Race Is Not Protective against Hazardous Bilirubin Levels. Pediatrics, 162, 1068-1069. [Google Scholar] [CrossRef] [PubMed]
[58] Okolie, F., South-Paul, J.E. and Watchko, J.F. (2020) Combating the Hidden Health Disparity of Kernicterus in Black Infants: A Review. JAMA Pediat-rics, 174, 1199-1205. [Google Scholar] [CrossRef] [PubMed]
[59] Bentz, M.G., Carmona, N., Bhagwat, M.M., et al. (2018) Beyond “Asian”: Specific East and Southeast Asian Races or Ethnicities Associated With Jaundice Readmission. Hospital Pediatrics, 8, 269-273. [Google Scholar] [CrossRef] [PubMed]
[60] Maruo, Y., Morioka, Y., Fujito, H., et al. (2014) Bilirubin Uridine Diphosphate-Glucuronosyitransferase Variation Is a Genetic Basis of Breast Milk Jaundice. The Journal of Pediatrics, 165, 36-41.e1. [Google Scholar] [CrossRef] [PubMed]
[61] Kuniyoshi, Y., Tokutake, H., Takahashi, N., et al. (2021) Regional Variation in the Development of Neonatal Hyperbilirubinemia and Relation with Sunshine Duration in Japan: An Eco-logical Study. The Journal of Maternal-Fetal & Neonatal Medicine, 1-6. [Google Scholar] [CrossRef] [PubMed]
[62] 阿日贡高娃, 白小丽. 蒙古族和汉族足月新生儿高胆红素血症发病情况及相关影响因素[J]. 中国妇幼保健, 2017, 32(11): 2372-2374.
[63] Raines, D.A., Krawiec, C. and Jain, S. (2022) Cephalohematoma. 2022 Feb 1. In: StatPearls, StatPearls Publishing, Treasure Island.
[64] Bergmann, A.U. and Thorkelsson, T. (2020) Incidence and Risk Factors for Severe Hyperbilirubinemia in Term Neonates. Laeknabladid, 106, 139-143. (Icelandic)
[65] Mojtahedi, S.Y., Izadi, A., Seirafi, G., et al. (2018) Risk Factors Associ-ated with Neonatal Jaundice: A Cross-Sectional Study from Iran. Open Access Open Access Macedonian Journal of Medical Sciences, 6, 1387-1393.