Progress on the impact of gestational diabetes mellitus on offspring neuropsychological development and its mechanisms

HUO Yunfeng; WU Juanjuan; WANG Hua

doi:10.11852/zgetbjzz2024-0899

PDF(586 KB)

Chinese Journal of Child Health Care ›› 2025, Vol. 33 ›› Issue (12) : 1338-1342. DOI: 10.11852/zgetbjzz2024-0899

Review

Progress on the impact of gestational diabetes mellitus on offspring neuropsychological development and its mechanisms

HUO Yunfeng¹, WU Juanjuan², WANG Hua¹

Author information +

History +

Abstract

Gestational diabetes mellitus (GDM) is a common pregnancy-related disorder that often leads to adverse pregnancy outcomes and may have long-term health implications for both mothers and their offspring.Neuropsychological studies on GDM-exposed offspring indicate an increased incidence of developmental delays, attention-deficit/hyperactivity disorder (ADHD), learning disabilities, and autism spectrum disorder (ASD).The mechanisms underlying GDM′s impact on offspring development involve multiple factors, including placental alterations during pregnancy, intrauterine oxidative stress, postnatal growth patterns, and changes in gene expression.Preconception and antenatal health management, along with regular developmental screening and early intervention after delivery, are essential measures for mothers with GDM and their children.This review summarizes the effects of GDM on offspring neuropsychological development, explores potential mechanisms, and proposes management recommendations.

Key words

gestational diabetes mellitus / neuropsychological development / health management / children

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

HUO Yunfeng, WU Juanjuan, WANG Hua. Progress on the impact of gestational diabetes mellitus on offspring neuropsychological development and its mechanisms[J]. Chinese Journal of Child Health Care. 2025, 33(12): 1338-1342 https://doi.org/10.11852/zgetbjzz2024-0899

References

[1] American Diabetes Association Professional Practice Committee.Management of diabetes in pregnancy: Standards of medical care in diabetes-2022[J].Diabetes Care,2022,45(Suppl 1):232-243.
[2] 中国2型糖尿病防治指南(2020年版)(下)[J].中国实用内科杂志,2021,41(9):757-784.
Chinese Guidelines for Prevention and Treatment of Type 2 Diabetes (2020 edition) (ii)[J].Chin J Practical Internal Med,2021,41(9):757-784.(in Chinese)
[3] Yefet E,Jeda Z,Yossef A,et al.Risk for fetal malformations and unfavorabl neonatal outcones in early-onset gestational diabetes mellitus[J].J Endocrinol Invest,2024,47(5):1181-1190.
[4] Tan J, Xiong Y, Wang X, et al.Influencing factors for postpartum depression in women with gestational diabetes mellitus[J].Front Endocrinol (Lausanne), 2024,15:1423127.
[5] Sweeting A,Wong J,Murphy HR,et al.A clinical update on gestational diabetes mellitus[J].Endocr Rev,2022,43(5):763-793.
[6] 张茜,余洁,肖新华.中国妊娠期糖尿病母儿共同管理指南(2024版)[J].中国研究型医院,2024,11(6),11-31.
Zhang Q,Yu J,Xiao XH.Guidelines for the joint management of gestational diabetes mellitus in China(2024 edition)[J].Chinese Journal of Research Hospital 2024,11(6):11-31.(in Chinese)
[7] Bateson P, Barker D, Clutton-Brock T, et al.Developmental plasticity and human health[J].Nature,2004,430(6998):419-421.
[8] Torres-Espinola FJ, Berglund SK, García-Valdés LM, et al.Maternal obesity, overweight and gestational diabetes affect the offspring neurodevelopment at 6 and 18 months of age--A follow up from the PREOBE cohort[J].PLoS One,2015;10(7):e0133010.
[9] He XJ, Dai RX, Tian CQ, et al.Neurodevelopmental outcome at 1 year in offspring of women with gestational diabetes mellitus[J].Gynecol Endocrinol,2021,37(1):88-92.
[10] DeBoer T, Wewerka S, Bauer PJ, et al.Explicit memory performance in infants of diabetic mothers at 1 year of age[J].Dev Med Child Neurol,2005,47(8):525-531.
[11] 陆青云,刘冰玥,肖静,等.妊娠期糖尿病合并孕前肥胖对子代18月龄神经智力发育的影响[J].南通大学学报(医学版),2019,39(3):170-174.
Lu QY, Liu BY, Xiao J, et al.Effect of gestational diabetes mellitus combined with preconception obesity on neurointelligence development of offspring at 18 months of age[J].J Nantong Univ,2019,39(3):170-174.(in Chinese)
[12] 袁灵皓,魏兵,岳小哲,等.沈阳市4~6岁儿童行为问题及其影响因素分析[J].中国儿童保健杂志,2022,30(4):436-440.
Yuan LH, Wei B, Yue XZ, et al.Analysis of behavior problems and influencing factors of children in Shenyang[J].Chin J Child Health Care,2022,30(4):436-440.(in Chinese)
[13] Guo D, Ju R, Zhou Q, et.al. Association of maternal diabetes with attention deficit/hyperactivity disorder (ADHD) in offspring: A Meta-analysis and review[J]. Diabetes Res Clin Pract,2020,165:108269.
[14] Chan AYL, Gao L, Hsieh MH,et.al.Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs[J].Nat Med,2024,30(5):1416-1423.
[15] Rivera HM, Christiansen KJ, Sullivan EL.The role of maternal obesity in the risk of neuropsychiatric disorders[J].Front Neurosci,2015,9:194.
[16] Xiang AH.Association of maternal diabetes with autism in offspring[J].JAMA,2017,317(5):537-538.
[17] Wan H, Zhang C, Li H, et al.Association of maternal diabetes with autism spectrum disorders in offspring: A systemic review and Meta-analysis[J].Medicine (Baltimore),2018,97(2):e9438.
[18] Aviel-Shekler K, Hamshawi Y, Sirhan W, et al.Gestational diabetes induces behavioral and brain gene transcription dysregulation in adult offspring[J].Transl Psychiatry,2020,10(1):412.
[19] Alves J, Yunker AG, DeFendis A, et al.Children′s anxiety and physical activity during COVID-19 in relation to prenatal exposure to gestational diabetes[J].medRxiv,2020:20169565.doi: 10.1101/2020.08.06.20169565.
[20] Bolaños L, Matute E, Ramírez-Due as Mde L, et al.Neuropsychological impairment in school-aged children born to mothers with gestational diabetes[J].J Child Neurol,2015,30(12):1616-1624.
[21] Ahmed S, Cano MÁ, Sánchez M, et al. Effect of exposure to maternal diabetes during pregnancy on offspring′s brain cortical thickness and neurocognitive functioning[J]. Child Neuropsychol,2023,29(4):588-606.
[22] Fraser A, Almqvist C, Larsson H, et al.Maternal diabetes in pregnancy and offspring cognitive ability: Sibling study with 723 775 men from 579 857 families[J].Diabetologia,2014,57(1):102-109.
[23] Huang S, Chen J, Cui Z, et al. Lachnospiraceae-derived butyrate mediates protection of high fermentable fiber against placental inflammation in gestational diabetes mellitus[J]. Sci Adv,2023,9(44):e7337.
[24] Katirci E, Kendirci-Katirci R, Korgun ET.Effects of stevioside on the expressions of GLUT 1, GLUT 3, and GLUT 4 proteins in diabetic rat placenta[J].Planta Med,2023,89(7):735-745
[25] Carrasco-Wong I, Moller A, Giachini FR, et al.Placental structure in gestational diabetes mellitus[J].Biochim Biophys Acta Mol Basis Dis,2020,1866(2):165535.
[26] Ozmen A, Kipmen-Korgun D, Korgun ET.Rapamycin administration during normal and diabetic pregnancy effects the mTOR and angiogenesis signaling in the rat placenta[J].J Gynecol Obstet Hum Reprod,2019,48(3):193-199.
[27] Thunbo M, Sinding M, Bogaard P, et al.Postpartum placental CT angiography in normal pregnancies and in those complicated by diabetes mellitus[J].Placenta,2018,69:20-25.
[28] Shi Y, Qian J, Zhang F, et al.Low molecular weight heparin (nadroparin) improves placental permeability in rats with gestational diabetes mellitus via reduction of tight junction factors[J].Mol Med Rep,2020,21(2):623-630.
[29] Sauer RS, Krug SM, Hackel D, et al.Safety, efficacy, and molecular mechanism of claudin-1-specific peptides to enhance blood-nerve-barrier permeability[J].J Control Release,2014,185:88-98.
[30] Kayama Y, Raaz U, Jagger A, et al.Diabetic cardiovascular disease induced by oxidative stress[J].Int J Mol Sci,2015,16(10):25234-25263.
[31] Ayer A, Fazakerley DJ, James DE, et al.The role of mitochondrial reactive oxygen species in insulin resistance[J].Free Radic Biol Med,2022,179:339-362.
[32] Han D, Jiang L, Gu X, et al.SIRT3 deficiency is resistant to autophagy-dependent ferroptosis by inhibiting the AMPK/mTOR pathway and promoting GPX4 levels[J].J Cell Physiol,2020,235(11):8839-8851.
[33] Tatar B, Turhan U.Increased sulfiredoxin-1 levels as compensatory mechanism against reactive oxygen species in women with gestational diabetes mellitus[J].Turk J Obstet Gynecol,2021,18(4):267-271.
[34] Bowers K, Yeung E, Williams MA, et al.A prospective study of prepregnancy dietary iron intake and risk for gestational diabetes mellitus[J].Diabetes Care,2011,34(7):1557-1563.
[35] Zhang Y, Lu Y, Jin L.Iron metabolism and ferroptosis in physiological and pathological pregnancy[J].Int J Mol Sci,2022,23(16):9395.
[36] Facco FL, Grobman WA, Reid KJ, et al.Objectively measured short sleep duration and later sleep midpoint in pregnancy are associated with a higher risk of gestational diabetes[J].Am J Obstet Gynecol,2017,217(4):447.
[37] Franzago M, Borrelli P, Di Nicola M, et al.From mother to child: Epigenetic signatures of hyperglycemia and obesity during pregnancy[J].Nutrients,2024,16(20):3502.
[38] Dimasuay KG, Boeuf P, Powell TL, et al.placental responses to changes in the maternal environment determine fetal growth[J].Front Physiol,2016,7:12.
[39] Zou JJ, Wei Q, Shi YY, et al.Longitudinal associations between maternal glucose levels and ultrasonographic fetal biometrics in a Shanghai Cohort[J].JAMA Netw Open,2022,5(4):e226407.
[40] Al Bekai E, Beaini CE, Kalout K, et al. The hidden impact of gestational diabetes: Unveiling offspring complications and long-term effects[J]. Life (Basel), 2025,15(3):440.
[41] Alatorre-Cruz GC, Downs H, Hagood D, et al.Effect of obesity on arithmetic processing in preteens with high and low math skills: An event-related potentials study[J].Front Hum Neurosci,2022,16:760234.
[42] Montaniel KRC, Bucher M, Phillips EA, et al.Dipeptidyl peptidase IV inhibition delays developmental programming of obesity and metabolic disease in male offspring of obese mothers[J].J Dev Orig Health Dis,2022,13(6):727-740.
[43] Sharma AK, Singh S, Singh H, et al. Deep insight of the pathophysiology of gestational diabetes mellitus[J]. Cells,2022,11(17):2672.
[44] Li HP, Chen X, Li MQ.Gestational diabetes induces chronic hypoxia stress and excessive inflammatory response in murine placenta[J].Int J Clin Exp Pathol, 2013,6(4):650-659.
[45] Li F, Zhang K, Liu H, et al.The neuroprotective effect of mesenchymal stem cells is mediated through inhibition of apoptosis in hypoxic ischemic injury[J].World J Pediatr,2020,16(2):193-200.
[46] Money KM, Barke TL, Serezani A, et al.Gestational diabetes exacerbates maternal immune activation effects in the developing brain[J].Mol Psychiatry,2018,23(9):1920-1928.
[47] 姜雪,孙文霞,齐艳.健康管理课程对妊娠期糖尿病孕妇生活方式及妊娠结局的影响[J].现代预防医学,2020,47(13):2364-2367.
Jiang X, Sun WX, Qi Y.Effect of health management course on life style and pregnancy outcome of pregnant women with gestational diabetes mellitus[J].Modern Preventive Med,2020,47(13):2364-2367.(in Chinese)