The Etiology of Fetal Growth Restriction and Its Effects on the Long-Term Health of the Child

doi:10.12280/gjfckx.20230840

Abstract

Abstract:

Fetal growth restriction (FGR) is one of the common and more complex complications of pregnancy, which refers to the inability of the fetus to reach its expected growth potential during pregnancy. The etiology of FGR is complex and varied, and may be caused by maternal, fetal or placental factors. Long-term follow-up studies of pediatric and adult patients with FGR have revealed adverse health outcomes. Fetuses with growth restriction lag significantly behind normal children in birth weight and length after delivery, and the vast majority of these children begin to experience significant growth catch-up early in life, but are at higher risk for metabolic problems. FGR is often associated with a range of long-term complications, such as neurologic deficits and abnormalities in skeletal muscle growth and metabolism, and is even associated with increased risk of metabolic syndrome and cardiovascular disease in adulthood. This has a serious impact on the physical health and quality of life of children with FGR. We summarize the pathogenic factors of FGR and its effects on the long-term health of children in order to provide theoretical support for the clinical prevention and treatment of FGR.

Key words: Fetal growth retardation, Embryonic development, Neurodevelopmental disorders, Musculoskeletal development, Metabolic syndrome

WANG Ya-hui, WANG Yan, WANG Yan, PEI Fe. The Etiology of Fetal Growth Restriction and Its Effects on the Long-Term Health of the Child[J]. Journal of International Obstetrics and Gynecology, 2024, 51(2): 152-156.

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References 42

[1]	Bendix I, Miller SL, Winterhager E. Editorial: Causes and Consequences of Intrauterine Growth Restriction[J]. Front Endocrinol(Lausanne), 2020, 11:205. doi: 10.3389/fendo.2020.00205.
[2]	Biesiada L, Sakowicz A, Grzesiak M, et al. Identification of placental genes linked to selective intrauterine growth restriction (IUGR) in dichorionic twin pregnancies: gene expression profiling study[J]. Hum Genet, 2019, 138(6):649-659. doi: 10.1007/s00439-019-02016-6. pmid: 31041507
[3]	隽娟, 杨慧霞. 胎儿生长受限对围产儿结局及远期健康的影响[J]. 中国实用妇科与产科杂志, 2020, 36(8):710-713. doi: 10.19538/j.fk2020080111.
[4]	Fetal Growth Restriction: ACOG Practice Bulletin, Number 227[J]. Obstet Gynecol, 2021, 137(2):e16-e28. doi: 10.1097/AOG.0000000000004251. pmid: 33481528
[5]	Eliner Y, Gulersen M, Kasar A, et al. Maternal and Neonatal Complications in Teen Pregnancies: A Comprehensive Study of 661,062 Patients[J]. J Adolesc Health, 2022, 70(6):922-927. doi: 10.1016/j.jadohealth.2021.12.014. pmid: 35165030
[6]	Karimi-Zarchi M, Zanbagh L, Javaheri A, et al. Association of Insulin-like Growth Factor-Ⅱ Apa1 and MspI Polymorphisms with Intrauterine Growth Restriction Risk[J]. Fetal Pediatr Pathol, 2021, 40(6):605-611. doi: 10.1080/15513815.2020.1745970.
[7]	Kulkarni VG, Sunilkumar KB, Nagaraj TS, et al. Maternal and fetal vascular lesions of malperfusion in the placentas associated with fetal and neonatal death: results of a prospective observational study[J]. Am J Obstet Gynecol, 2021, 225(6):660.e1-e12. doi: 10.1016/j.ajog.2021.06.001.
[8]	Ip S, Griffin A, Lourie R, et al. Chronic villitis of unknown aetiology: an Australian institution′s 5-year experience[J]. Pathology, 2022, 54(7):882-887. doi: 10.1016/j.pathol.2022.03.015.
[9]	Eggenhuizen GM, Go A, Koster M, et al. Confined placental mosaicism and the association with pregnancy outcome and fetal growth: a review of the literature[J]. Hum Reprod Update, 2021, 27(5):885-903. doi: 10.1093/humupd/dmab009. pmid: 33984128
[10]	Fung C, Zinkhan E. Short- and Long-Term Implications of Small for Gestational Age[J]. Obstet Gynecol Clin North Am, 2021, 48(2):311-323. doi: 10.1016/j.ogc.2021.02.004.
[11]	Hong J, Kumar S. Circulating biomarkers associated with placental dysfunction and their utility for predicting fetal growth restriction[J]. Clin Sci(Lond), 2023, 137(8):579-595. doi: 10.1042/CS20220300.
[12]	牟秋杰, 嵇波, 赵国桢, 等. 电针对孕期饮食限制诱发宫内生长受限大鼠肺发育不良的影响[J]. 中国针灸, 2021, 41(4):405-410. doi: 10.13703/j.0255-2930.20200507-k0008.
[13]	Dai Y, Zhao D, Chen CK, et al. Echocardiographic assessment of fetal cardiac function in the uterine artery ligation rat model of IUGR[J]. Pediatr Res, 2021, 90(4):801-808. doi: 10.1038/s41390-020-01356-8. pmid: 33504964
[14]	Matre M, Mehl CV, Benum SD, et al. Body composition and physical fitness in adults born small for gestational age at term: a prospective cohort study[J]. Sci Rep, 2023, 13(1):3455. doi: 10.1038/s41598-023-30371-y. pmid: 36859477
[15]	Stróżewska W, Durda-Masny M, Szwed A. Mutations in GHR and IGF1R Genes as a Potential Reason for the Lack of Catch-Up Growth in SGA Children[J]. Genes(Basel), 2022, 13(5):856. doi: 10.3390/genes13050856.
[16]	Hesse H, Palmer C, Rigdon CD, et al. Differences in body composition and growth persist postnatally in fetuses diagnosed with severe compared to mild fetal growth restriction[J]. J Neonatal Perinatal Med, 2022, 15(3):589-598. doi: 10.3233/NPM-210872. pmid: 35342050
[17]	侯留杰, 栗河舟, 吴娟, 等. 颅脑超声评估宫内生长受限对新生儿脑发育的影响[J]. 中国医学影像学杂志, 2022, 30(3):261-265. doi: 10.3969/j.issn.1005-5185.2022.03.014.
[18]	张伊佳. 宫内生长受限对神经系统结构和功能影响的研究进展[J]. 中国当代儿科杂志, 2021, 23(11):1184-1189. doi: 10.7499/j.issn.1008-8830.2108044.
[19]	Brown AS, Wieben M, Murdock S, et al. Intrauterine Growth Restriction Causes Abnormal Embryonic Dentate Gyrus Neurogenesis in Mouse Offspring That Leads to Adult Learning and Memory Deficits[J]. eNeuro, 2021, 8(5): ENEURO.0062-21.2021. doi: 10.1523/ENEURO.0062-21.2021.
[20]	Pla L, Illa M, Loreiro C, et al. Structural Brain Changes during the Neonatal Period in a Rabbit Model of Intrauterine Growth Restriction[J]. Dev Neurosci, 2020, 42(5/6):217-229. doi: 10.1159/000512948.
[21]	王京京, 付正英, 张引国. Cofilin、CREB及P38/MAPK分子信号与宫内生长受限大鼠学习记忆障碍的关系[J]. 武警后勤学院学报(医学版), 2017, 26(2):99-103.
[22]	石莉, 符小艳, 王丽, 等. 正常与宫内生长受限胎儿神经系统发育产前超声监测[J]. 中山大学学报(医学科学版), 2020, 41(5):767-773.
[23]	Xu B, Liu C, Zhang H, et al. Skeletal muscle-targeted delivery of Fgf6 protects mice from diet-induced obesity and insulin resistance[J]. JCI Insight, 2021, 6(19):e149969. doi: 10.1172/jci.insight.149969.
[24]	Stremming J, Jansson T, Powell TL, et al. Reduced Na⁺ K⁺ -ATPase activity may reduce amino acid uptake in intrauterine growth restricted fetal sheep muscle despite unchanged ex vivo amino acid transporter activity[J]. J Physiol, 2020, 598(8):1625-1639. doi: 10.1113/JP278933.
[25]	Gibbs RL, Yates DT. The Price of Surviving on Adrenaline: Developmental Programming Responses to Chronic Fetal Hypercatecholaminemia Contribute to Poor Muscle Growth Capacity and Metabolic Dysfunction in IUGR-Born Offspring[J]. Front Anim Sci, 2021, 2:769334. doi: 10.3389/fanim.2021.769334.
[26]	Li P, He L, Lan Y, et al. Intrauterine Growth Restriction Induces Adulthood Chronic Metabolic Disorder in Cardiac and Skeletal Muscles[J]. Front Nutr, 2022, 9:929943. doi: 10.3389/fnut.2022.929943.
[27]	唐本玉, 陈丹纯, 郭蕾, 等. 宫内发育迟缓雌性仔鼠早期营养对生长追赶的影响[J]. 中山大学学报(医学科学版), 2019, 40(4):532-539.
[28]	Sreekantha S, Wang Y, Sakurai R, et al. Maternal food restriction-induced intrauterine growth restriction in a rat model leads to sex-specific adipogenic programming[J]. FASEB J, 2020, 34(12):16073-16085. doi: 10.1096/fj.202000985RR. pmid: 33047380
[29]	Gantenbein KV, Kanaka-Gantenbein C. Highlighting the trajectory from intrauterine growth restriction to future obesity[J]. Front Endocrinol(Lausanne), 2022, 13:1041718. doi: 10.3389/fendo.2022.1041718.
[30]	Andermann ML, Lowell BB. Toward a Wiring Diagram Understanding of Appetite Control[J]. Neuron, 2017, 95(4):757-778. doi: 10.1016/j.neuron.2017.06.014. pmid: 28817798
[31]	Castro-Barquero S, Ruiz-León AM, Sierra-Pérez M, et al. Dietary Strategies for Metabolic Syndrome: A Comprehensive Review[J]. Nutrients, 2020, 12(10):2983. doi: 10.3390/nu12102983.
[32]	Cheng K, Yu C, Li Z, et al. Resveratrol improves meat quality, muscular antioxidant capacity, lipid metabolism and fiber type composition of intrauterine growth retarded pigs[J]. Meat Sci, 2020, 170:108237. doi: 10.1016/j.meatsci.2020.108237.
[33]	Keshavjee B, Lambelet V, Coppola H, et al. Stress-Induced Premature Senescence Related to Oxidative Stress in the Developmental Programming of Nonalcoholic Fatty Liver Disease in a Rat Model of Intrauterine Growth Restriction[J]. Antioxidants(Basel), 2022, 11(9):1695. doi: 10.3390/antiox11091695.
[34]	卞京, 陈平洋, 卞读军, 等. Lipin基因表达与宫内发育迟缓大鼠肝脏脂肪含量的相关性研究[J]. 中国当代儿科杂志, 2022, 24(4):440-446. doi: 10.7499/j.issn.1008-8830.2110130.
[35]	Liefke J, Steding-Ehrenborg K, Sjöberg P, et al. Higher blood pressure in adolescent boys after very preterm birth and fetal growth restriction[J]. Pediatr Res, 2023, 93(7):2019-2027. doi: 10.1038/s41390-022-02367-3.
[36]	Visentin S, Londero AP, Calanducci M, et al. Fetal Abdominal Aorta: Doppler and Structural Evaluation of Endothelial Function in Intrauterine Growth Restriction and Controls[J]. Ultraschall Med, 2019, 40(1):55-63. doi: 10.1055/s-0043-122230. pmid: 30253430
[37]	Li M, Zhang Z, Joynauth J, et al. Intrauterine growth restriction neonates present with increased angiogenesis through the Notch1 signaling pathway[J]. Microvasc Res, 2022, 140:104308. doi: 10.1016/j.mvr.2021.104308.
[38]	Bhunu B, Riccio I, Intapad S. Insights into the Mechanisms of Fetal Growth Restriction-Induced Programming of Hypertension[J]. Integr Blood Press Control, 2021, 14:141-152. doi: 10.2147/IBPC.S312868.
[39]	Sehgal A, Alexander BT, Morrison JL, et al. Fetal Growth Restriction and Hypertension in the Offspring: Mechanistic Links and Therapeutic Directions[J]. J Pediatr, 2020, 224:115-123.e2. doi: 10.1016/j.jpeds.2020.05.028.
[40]	Mutamba AK, He X, Wang T. Therapeutic advances in overcoming intrauterine growth restriction induced metabolic syndrome[J]. Front Pediatr, 2022, 10:1040742. doi: 10.3389/fped.2022.1040742.
[41]	袁冰舒, 李丽娟. 肠道菌群改变影响CG-IUGR大鼠糖代谢的初步研究[J]. 天津医药, 2023, 51(12):1307-1313. doi: 10.11958/20230026.
[42]	Luo D, Mu T, Sun H. Sweet potato (Ipomoea batatas L.) leaf polyphenols ameliorate hyperglycemia in type 2 diabetes mellitus mice[J]. Food Funct, 2021, 12(9):4117-4131. doi: 10.1039/d0fo02733b.

分类	致病因素
母体因素	孕前糖尿病、肾功能不全、自身免疫性疾病、紫绀性心脏病、慢性高血压、子痫前期、妊娠期高血压、母体营养不良、抗磷脂抗体综合征、获得性免疫介导血栓形成倾向、物质滥用（如烟草、酒精、可卡因、麻醉剂）、暴露于致畸物（如环磷酰胺、丙戊酸、抗血栓药）等
胎儿因素	染色体异常（13、18、21-三体综合征）、先天性心脏病、腹裂、胎儿感染（如巨细胞病毒、风疹、单纯疱疹、艾滋病毒、梅毒、疟疾、弓形虫）、多胎妊娠、胎产次等
胎盘因素	胎盘功能不全、胎盘早剥、胎盘梗死、轮状胎盘、胎盘血管瘤、绒毛血管瘤、脐带异常（如过长、过细、扭曲、真结、单脐动脉、扁平脐带、脐带帆状附着、胎盘边缘附着）等

分类	致病因素
母体因素	孕前糖尿病、肾功能不全、自身免疫性疾病、紫绀性心脏病、慢性高血压、子痫前期、妊娠期高血压、母体营养不良、抗磷脂抗体综合征、获得性免疫介导血栓形成倾向、物质滥用（如烟草、酒精、可卡因、麻醉剂）、暴露于致畸物（如环磷酰胺、丙戊酸、抗血栓药）等
胎儿因素	染色体异常（13、18、21-三体综合征）、先天性心脏病、腹裂、胎儿感染（如巨细胞病毒、风疹、单纯疱疹、艾滋病毒、梅毒、疟疾、弓形虫）、多胎妊娠、胎产次等
胎盘因素	胎盘功能不全、胎盘早剥、胎盘梗死、轮状胎盘、胎盘血管瘤、绒毛血管瘤、脐带异常（如过长、过细、扭曲、真结、单脐动脉、扁平脐带、脐带帆状附着、胎盘边缘附着）等