辅助生殖技术受孕儿童健康状况的研究进展

Advances in health status of children conceived through assisted reproductive technology

摘要

辅助生殖技术(ART)自1978年问世以来,为治疗不孕不育开创了新时代。目前ART在全球广泛应用,累计已诞生超过1 000万名ART受孕儿童。ART子代的健康状况和生活质量已成为全球医学界及社会各界关注的重要公共卫生问题。本文综述了近年来国内外关于ART受孕儿童健康状况的研究,重点探讨围产期结局、子代代谢状况及行为认知发育是否存在风险。结果显示,目前多数研究认为ART受孕儿童整体健康状况良好。建议推广单胚胎移植以减少多胎妊娠,从源头降低ART儿童围生期并发症及神经发育异常的风险;同时应持续关注其长期健康状况,为优化相关人群的医疗保健提供科学依据。

Abstract

Since the advent of assisted reproductive technology (ART) in 1978, a new era has been opened for infertility management. Currently, ART is widely implemented across the globe, with over 10 million children born to date. The health status and quality of life of ART offspring have evolved into a critical public health concern, drawing extensive attention from the global medical community and society. This paper reviews recent domestic and international research on the health outcomes of ART-conceived children, with a specific focus on three core domains: perinatal outcomes, metabolic status, and potential risks associated with behavioral and cognitive development. Synthesis of the evidence indicates that the overall health status of ART-conceived children is favorable. It is recommended that single embryo transfer be prioritized to reduce multiple pregnancies, thereby mitigating the risks of perinatal complications and neurodevelopmental abnormalities at the source. Meanwhile, sustained surveillance of long-term health trajectories is warranted to facilitate the optimization of healthcare services for this population.

关键词

辅助生殖技术 / 糖代谢 / 脂代谢 / 神经发育 / 儿童

Key words

assisted reproductive technology / glucose metabolism / lipid metabolism / neural development / children

[1] Feng J, Wu Q, Liang Y, et al. Epidemiological characteristics of infertility, 1990–2021, and 15-year forecasts: An analysis based on the global burden of disease study 2021[J]. Reprod Health, 2025, 22(1): 26.
[2] Gliozheni O, Hambartsoumian E, Strohmer H, et al. ART in Europe, 2019:Results generated from European registries by ESHRE[J]. Hum Reprod, 2023, 38(12): 2321-2338.
[3] Stern JE, Farland LV, Hwang SS, et al. Assistedreproductive technology or infertility: What underlies adverse outcomes? Lessons from the Massachusetts Outcome Study of Assisted Reproductive Technology[J]. F S Rev, 2022, 3(4): 242-255.
[4] Penova-Veselinovic B, Wijs LA, Yovich JL, et al. Cohort profile: The Growing Up Healthy Study (GUHS)—a prospective and observational cohort study investigating the long-term health outcomes of offspring conceived after assisted reproductive technologies[J]. PLoS One, 2022, 17(7): e0272064.
[5] Waldaufova E, Stastna A, Fait T. The low birth weights of newborns conceived using assisted reproduction technology[J].Bratislava Med J, 2024, 125(2): 137-143.
[6] 胡丹, 汪晓霞, 崔一帆等. 辅助生殖技术试管足月儿神经心理行为发育的纵向研究 [J]. 中国儿童保健杂志, 2022, 30(2): 140-143.
Hu D,Wang XX,Cui YF,et al.Longitudinal study on neuropsychological and behavioral development of test-tube full-term infants with assisted reproduction technology[J].Chin J Child Health Care,2022,30(2):140-143.(in Chinese)
[7] 胡丹, 汪晓霞, 崔一帆等. 辅助生殖技术受孕单胎早产儿出生结局和认知发育的纵向研究 [J]. 中国儿童保健杂志, 2022, 30(6): 669-672.
Hu D,Wang XX,Cui YF,et al.Longitudinal study on the birth outeome and cognitive development of singleton preterm infants conceived by assisted reproduction technology[J].Chin J Child Health Care,2022,30(6):669-672.(in Chinese)
[8] Angel P, Hermansen M, Ramlau-Hansen CH, et al. Neurodevelopmental or behavioral disorders in children conceived after assisted reproductive technologies: A nationwide cohort study[J]. Fertil Steril, 2025, 123(4): 665-676.
[9] Ohuma EO, Moller AB, Bradley E, et al. National, regional, and global estimates of preterm birth in 2020, with trends from 2010:A systematic analysis[J]. Lancet, 2023, 402(10409): 1261-1271.
[10] Tocariu R, Dinulescu A, Prejmereanu A, et al. Riskfactors for prematurity and congenital malformations in assisted reproductive technology pregnancies—a retrospective study[J]. J Clin Med, 2024, 13(21): 6470.
[11] Langer M, Vilsmaier T, Kramer M, et al. Vascularhealth in adults born after using assisted reproductive technologies[J]. Pediatr Cardiol, 2024, 45(6): 1242-1250.
[12] Li W, Zhao J, Ni M, et al. Assisted reproductive technology and neurodevelopmental outcomes in offspring:A prospective birth cohort study in East China[J]. Reprod BioMed Online, 2023, 46(6): 983-994.
[13] Pinborg A, WennerholmUB, Bergh C. Long-term outcomes for children conceived by assisted reproductive technology[J]. Fertil Steril, 2023, 120(3): 449-456.
[14] Purkayastha M, Roberts SA, Gardiner J, et al. Cohort profile:A national, population-based cohort of children born after assisted conception in the UK (1992–2009): Methodology and birthweight analysis[J]. BMJ Open, 2021, 11(7): e050931.
[15] Wang J, Chen L, Yong Y, et al. Comprehensivehealth assessment of school-age children conceived by assisted reproductive technology: A prospective cohort follow-up study[J]. BJOG, 2025, 132(S2): 8-17.
[16] OlsenAR, Asserhøj LL, Pinborg A, et al. Visceral and subcutaneous adipose tissue in children born after ART with frozen and fresh embryo transfers[J]. Hum Reprod Open, 2025, 2025(2): hoaf014.
[17] Ono M, Kuji N, Ueno K, et al. Thelong-term outcome of children conceived through assisted reproductive technology[J]. Reprod Sci, 2024, 31(3): 583-590.
[18] Rumbold AR, Sevoyan A, Oswald TK, et al. Impact of male factor infertility on offspring health and development[J].Fertil Steril, 2019, 111(6): 1047-1053.
[19] Laugesen K, Veres K, Hernandez-Diaz S, et al. Overweight or obesity in children born after assisted reproductive technologies in Denmark: A population-based cohort study[J]. PLoS Med, 2023, 20(12): e1004324.
[20] Norrman E, Petzold M, Gissler M, et al. Cardiovascular disease, obesity, and type 2 diabetes in children born after assisted reproductive technology: A population-based cohort study[J]. PLoS Med, 2021, 18(9): e1003723.
[21] Matsumoto N, Mitsui T, Kadowaki T, et al.In vitro fertilization and long-term child health and development: Nationwide birth cohort study in Japan[J]. Eur J Pediatr, 2024, 184(1): 24.
[22] McMillen IC, MacLaughlin SM, Muhlhausler BS, et al. Developmental origins of adult health and disease:The role of periconceptional and foetal nutrition [J]. Basic Clin Pharmacol Toxicol, 2008, 102(2): 82-89.
[23] Sciorio R,El Hajj N. Epigenetic risks of medically assisted reproduction[J]. J Clin Med, 2022, 11(8): 2151.
[24] Graham ME, Jelin A, Hoon AH Jr, et al. Assisted reproductive technology: Short- and long-term outcomes [J]. Dev Med Child Neurol, 2023, 65(1): 38-49.
[25] Wahl S, Drong A, Lehne B, et al. Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity [J]. Nature, 2017, 541(7635): 81-86.
[26] Duranthon V, Chavatte-Palmer P. Long term effects of ART: What do animals tell us?[J]. Mol Reprod Dev, 2018, 85(4): 348-368.
[27] Collaborators G A B. Global, regional, and national prevalence of adult overweight and obesity, 1990-2021, with forecasts to 2050:A forecasting study for the Global Burden of Disease Study 2021 [J]. Lancet, 2025, 405(10481): 813-838.
[28] MagnusMC, Wilcox AJ, Fadum EA, et al. Growth in children conceived by ART[J]. Hum Reprod, 2021, 36(4): 1074-1082.
[29] Chen F, Huang K, Long Q, et al. Comparative dietary effectiveness of a modified government-recommended diet with avoidance of ultra-processed foods on weight and metabolic management in children and adolescents: An open-label, randomized study [J]. Asia Pac J Clin Nutr, 2022, 31(2): 282293.
[30] Elhakeem A, TaylorAE, Inskip HM, et al. Long-term cardiometabolic health in people born after assisted reproductive technology: A multi-cohort analysis[J]. Eur Heart J, 2023, 44(16): 1464-1473.
[31] Gu L, Zhang J, Zheng M, et al. A potential high risk for fatty liver disease was found in mice generated after assisted reproductive techniques[J].J Cell Biochem, 2018, 119(2): 1899-1910.
[32] Narapareddy L, Rhon-CalderonEA, Vrooman LA, et al. Sex-specific effects of in vitro fertilization on adult metabolic outcomes and hepatic transcriptome and proteome in mouse[J]. FASEB J, 2021, 35(4): e21523.
[33] Rabinowicz S, Levkovitz O, Leibovitch L, et al. Increased risk for early hypertriglyceridemia in small for gestational age preterm infants[J].Eur J Pediatr, 2020, 179(12): 1873-1879.
[34] García-Domínguez X, Diretto G, Peñaranda DS, et al. Early embryo exposure to assisted reproductive manipulation induced subtle changes in liver epigenetics with No apparent negative health consequences in rabbit[J]. Int J Mol Sci, 2021, 22(18): 9716.
[35] Asserhøj LL, Mizrak I, Lebech Kjaer AS, et al. Blood pressure and lipid profiles in children born after ART with frozen embryo transfer[J]. Hum Reprod Open, 2024, 2024(2): hoae016.
[36] GuoXY, Liu XM, Jin L, et al. Cardiovascular and metabolic profiles of offspring conceived by assisted reproductive technologies: A systematic review and meta-analysis[J]. Fertil Steril, 2017, 107(3): 622-631.e5.
[37] Kyhl F, Spangmose AL, Gissler M, et al. The risk of Type 1 diabetes in children born after ART: A Nordic cohort study from the CoNARTaS group[J]. Hum Reprod Open, 2024, 2024(2): hoae021.
[38] Cui L, Zhou W, Xi B, et al. Increased risk of metabolic dysfunction in children conceived by assisted reproductive technology[J]. Diabetologia, 2020, 63(10): 2150-2157.
[39] Ban M, Feng W, Hou M, et al. IVF exposure induced intergenerational effects on metabolic phenotype in mice [J]. Reprod Biomed Online, 2024, 49(3): 103992.
[40] Cerny D, Sartori C, Rimoldi SF, et al. Assistedreproductive technologies predispose to insulin resistance and obesity in male mice challenged with a high-fat diet[J]. Endocrinology, 2017, 158(5): 1152-1159.
[41] Morrison KM, Ramsingh L, Gunn E, et al. Cardiometabolichealth in adults born premature with extremely low birth weight[J]. Pediatrics, 2016, 138(4): e20160515.
[42] TolaniAT, Cedars MI, Zablotska LB, et al. Metabolomic profile of children conceived with medically assisted technologies[J]. J Clin Endocrinol Metab, 2023, 108(2): 315-322.
[43] Zhao J, Li S, Ban M, et al. Metabolicprofiles of offspring born from biopsied embryos from toddlerhood to preschool age[J]. J Clin Endocrinol Metab, 2025, 110(4): e980-e991.
[44] Farhi A, GabisLV, Frank S, et al. Cognitive achievements in school-age children born following assisted reproductive technology treatments: A prospective study[J]. Early Hum Dev, 2021, 155: 105327.
[45] Acharyya S,Acharyya K. A cohort study comparing the growth and neurodevelopmental outcome of babies conceived by assisted reproductive technology with those of naturally conceived babies from birth till 24 months[J]. Indian J Pediatr, 2023, 90(1): 16-21.
[46] Wagenaar K, van Weissenbruch MM, Knol DL, et al. Information processing, attention and visual-motor function of adolescents born after in vitro fertilization compared with spontaneous conception[J]. Hum Reprod, 2008, 24(4): 913-921.
[47] Vo MT, Le TMC, Le TQ, et al. Comparison of psychomotor development among children conceived through icsi in-vitro-fertilisation and naturally at 5 through 30 months of age, Vietnam[J].Eur J Obstet Gynecol Reprod Biol, 2021, 258: 157-161.
[48] Wienecke LS, Kjær SK, Frederiksen K, et al. Ninth-grade school achievement in Danish children conceived following fertility treatment:A population-based cohort study[J]. Fertil Steril, 2020, 113(5): 1014-1023.
[49] Norrman E, Petzold M, Bergh C, et al. School performance in singletons born after assisted reproductive technology[J].Hum Reprod, 2018, 33(10): 1948-1959.
[50] Barbuscia A,Mills MC. Cognitive development in children up to age 11 years born after ART—a longitudinal cohort study[J]. Hum Reprod, 2017, 32(7): 1482-1488.
[51] Rönö K, Rissanen E, Bergh C, et al. The neurodevelopmental morbidity of children born after assisted reproductive technology:A Nordic register study from the Committee of Nordic Assisted Reproductive Technology and Safety group[J]. Fertil Steril, 2022, 117(5): 1026-1037.
[52] Fountain C, Zhang Y, Kissin DM, et al. Association between assisted reproductive technology conception and autism in California, 1997–2007[J]. Am J Public Health, 2015, 105(5): 963-971.
[53] Sandin S, Schendel D, Magnusson P, et al. Autism risk associated with parental age and with increasing difference in age between the parents[J]. Mol Psychiatry, 2016, 21(5): 693-700.
[54] Winter AS, Yartel AK, Fountain C, et al. The role of multiple birth and birth complications in the association between assisted reproductive technology conception and autism diagnosis[J].Am J Epidemiol, 2024, 193(10): 1426-1432.

基金资助

大连市妇女儿童医疗中心(集团)博士启动基金项目(2022年)