辅助生殖技术受孕单胎儿童在学龄前期代谢状况的研究

Metabolic status of singleton preschool children conceived by assisted reproductive technology

摘要

目的 比较辅助生殖技术(ART)受孕单胎学龄前儿童与自然受孕(NC)单胎儿童的代谢状况,为促进ART儿童的健康管理提供依据。方法 采用病例对照研究,选取2023年1月—2025年1月于大连市妇女儿童医疗中心(集团)儿童保健门诊体检的36~72月龄ART受孕单胎儿童70例,并按1∶1纳入同期年龄匹配的NC单胎儿童70例作为对照。收集父母一般资料、围生期信息及儿童喂养饮食情况,测量身高、体重、腰围、血压,并检测空腹血糖(FBG)、空腹胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白A1(ApoA1)和载脂蛋白B(ApoB)等指标。采用多元线性回归对饮食因素及父母BMI等混杂因素进行调整。结果 ART组父母生育年龄高于NC组,孕期体重增长低于NC组(t=6.761、6.032,-2.329,P<0.05)。调整混杂因素后,两组儿童体重、身高、BMI及血压差异均无统计学意义(P>0.05),但ART组腰围高于NC组(β=2.022,P<0.05)。血液生化指标比较显示,调整后ART组TG、ApoB高于NC组(β=0.104、0.038,P<0.05),HDL-C、ApoA1低于NC组(β=-0.298、-0.105,P<0.05),而TC、LDL-C、FBG、FINS及HOMA-IR差异均无统计学意义(P>0.05)。两组血压异常、血脂异常及血糖异常检出率差异均无统计学意义(P>0.05);ART组超重/肥胖检出率高于NC组(Z=-2.233,P<0.05)。结论 学龄前期ART单胎儿童在部分血脂指标(TG、HDL-C、ApoB、ApoA1)与NC组儿童存在差异。但未表现出血脂异常风险增加,ART组腰围、儿童肥胖、超重发生率均较NC组偏高,提示应加强对ART单胎儿童营养状况及代谢指标的长期监测,预防肥胖及相关代谢性疾病的发生发展。

Abstract

Objective To compare the metabolic status of preschool singleton children conceived by assisted reproductive technology (ART) with naturally conceived (NC) singleton children, so as to provide evidence for the health management of ART-conceived children. Methods A total of 70 ART-conceived singleton children aged 36 - 72 months who underwent physical examination at the Dalian Women and Children's Medical Group from January 2023 to January 2025 were enrolled, and 70 age-matched NC singleton children were included at a 1∶1 ratio during the same period. Parental demographics, perinatal information, and the children's feeding and dietary habits were collected. Anthropometric measurements (height, weight, waist circumference) and blood pressure were assessed. Fasting blood glucose (FBG), fasting insulin (FINS), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB) levels were measured. Multiple linear regression models were employed to adjust for potential confounding factors, including dietary habits and parental body mass index (BMI). Results Parents in the ART group had significantly older reproductive ages and lower gestational weight gain than those in the NC group (t=6.761, 6.032,-2.329, P<0.05). After adjustment for confounding factors, there were no statistically significant differences in body weight, height, body mass index, or blood pressure between the two groups (P>0.05). However, waist circumference was significantly greater in the ART group than in the NC group (β=2.022, P<0.05). After adjustment, TG and ApoB levels remained significantly higher in the ART group(β=0.104,0.038), while HDL-C and ApoA1 levels were significantly lower than those in the NC group (β=-0.298,-0.105,P<0.05). No significant differences were found in TC, LDL-C, FBG, FINS, or HOMA-IR between the two groups (P>0.05). There were no significant differences in the detection rates of abnormal blood pressure, dyslipidemia, or impaired blood glucose between the two groups (P>0.05). The detection rate of overweight/obesity was significantly higher in the ART group than in the NC group (Z=-2.233, P<0.05). Conclusions Preschool singleton children conceived by ART exhibit differences in several blood lipid parameters, including TG, HDL-C, ApoB, and ApoA1. However, these differences do not increase the risk of dyslipidemia. Increased waist circumference and a higher prevalence of overweight/obesity are observed in ART-conceived children, highlighting the importance of long-term monitoring of nutritional and metabolic status in this population to prevent obesity and related metabolic disorders.

关键词

辅助生殖技术 / 单胎儿童 / 学龄前期 / 代谢状况

Key words

assisted reproductive technology / singleton children / preschool age / metabolic status

[1] 黄荷凤. 实用人类辅助生殖技术[M]. 北京: 人民卫生出版社, 2018.
[2] 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.
[3] Le F, Lou HY, Wang QJ, et al. Increased hepatic INSIG-SCAP-SREBP expression is associated with cholesterol metabolism disorder in assisted reproductivetechnology-conceived aged mice[J]. Reprod Toxicol, 2019, 84: 9-17.
[4] 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(Suppl 2): 8-17.
[5] Marleen S, Kodithuwakku W, Nandasena R, et al. Maternal and perinatal outcomes in twin pregnancies following assisted reproduction:A systematic review and meta-analysis involving 802 462 pregnancies[J]. Hum Reprod Update, 2024, 30(3): 309-322.
[6] Garner J, Parisaei M, Shah A. Re: Obstetric and neonatal complications in pregnancies conceived after oocyte donation:A systematic review and meta-analysis: Significance of advising women prior to fertility treatment[J]. BJOG, 2017, 124(9): 1451-1452.
[7] 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.
[8] 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.
[9] Ajeen R, Turk-Adawi KI, Ammerman AS, et al. Assessing the relationship between anthropometric indices and visceral adipose tissue: A cross-sectional study in a Qatari population[J]. J Int Med Res, 2025, 53(9): 3000605251371603.
[10] Ross R, Neeland IJ, Yamashita S, et al. Waist circumference as a vital sign in clinical practice:A Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity[J]. Nat Rev Endocrinol, 2020, 16(3): 177-189.
[11] Ono M, Kuji N, Ueno K, et al. The long-term outcome of children conceived through assisted reproductive technology[J]. Reprod Sci, 2024, 31(3): 583-590.
[12] Langer M, Vilsmaier T, Kramer M, et al. Vascular health in adults born after using assisted reproductive technologies[J]. Pediatr Cardiol, 2024, 45(6): 1242-1250.
[13] Zhang S, Luo Q, Meng R, et al. Long-term health risk of offspring born from assisted reproductive technologies[J].J Assist Reprod Genet, 2024, 41(3): 527-550.
[14] Ilmuratova S, Manzhuova L, Bazarbayeva A, et al. Focus on the endocrine system of children born after reproductive technologies in Kazakhstan[J]. Qatar Med J, 2025, 2025(1): 9.
[15] Narapareddy L, Rhon-Calderon EA, 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.
[16] Wu W, Ji M, Yang J, et al. ART altered DNA methylation of the imprinted gene H19 in fetal tissue after multifetal pregnancy reduction[J].J Assist Reprod Genet, 2024, 41(11): 3039-3049.
[17] 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.
[18] 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.
[19] Mendelson MM, Marioni RE, Joehanes R, et al. Association ofbody mass index with DNA methylation and gene expression in blood cells and relations to cardiometabolic disease: A Mendelian randomization approach[J]. PLoS Med, 2017, 14(1): e1002215.
[20] 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.
[21] Cui Y, Wang Y, Wang X, et al. Metabolicstatus and expression level of SREBP mRNA and mir-33 among children conceived by assisted reproductive technology[J]. Int J Genomics, 2025, 2025: 2271298.
[22] Catford SR, McLachlan RI, O'Bryan MK, et al. Long-term follow-up of ICSI-conceived offspring compared with spontaneously conceived offspring: A systematic review of health outcomes beyond the neonatal period[J]. Andrology, 2018, 6(5): 635-653.
[23] Wijs LA, Doherty DA, Keelan JA, et al. Comparison of the cardiometabolic profiles of adolescents conceived through ART with those of a non-ART cohort[J]. Hum Reprod,2022, 37(8): 1880-1895.

基金资助

肖绪武,E-mail:[e-mail]