Epidemiological review of the association between maternal metabolic syndrome and obesity and neurodevelopmental disorders in children

  • Vladica Žikić Cognitive Neuroscience Department, Research and Development Institute “Life Activities Advancement Institute”, Belgrade, Serbia https://orcid.org/0000-0002-2570-4464
  • Vesna Vučić Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of the Republic of Serbia, Belgrade, Serbia
  • Aleksandra Veselinović Cognitive Neuroscience Department, Research and Development Institute “Life Activities Advancement Institute”, Belgrade, Serbia and Department of Speech, Language and Hearing Sciences, Institute for Experimental Phonetics and Speech Pathology, Belgrade, Serbia
  • Miško Subotić Cognitive Neuroscience Department, Research and Development Institute “Life Activities Advancement Institute”, Belgrade, Serbia and Department of Speech, Language and Hearing Sciences, Institute for Experimental Phonetics and Speech Pathology, Belgrade, Serbia
  • Marija Radovanović Pediatric Clinic, Clinical Center, Kragujevac, Serbia and University of Kragujevac, Faculty of Medical Sciences, Department of Pediatrics, Kragujevac, Serbia
  • Danijela Ristić-Medić Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, National Institute of the Republic of Serbia, Belgrade, Serbia
Keywords: Metabolic syndrome, obesity, neurodevelopmental disorders

Abstract


Introduction. Maternal metabolic syndrome is becoming increasingly recognized as a significant factor that can affect the health and development of children. Aim. This study investigates how MetS during pregnancy can increase the risk of obesity and neurodevelopmental disorders in children. Method. By reviewing various studies and recent data, we found that high blood sugar levels, insulin resistance, and chronic inflammation during pregnancy can lead to the stated issues. Results. This review paper indicates that addressing metabolic health in pregnant women early on can greatly reduce these risks and improve long-term health outcomes for their children. Conclusion. This study emphasizes the importance of comprehensive prenatal care that focuses on metabolic health to help prevent childhood obesity and neurodevelopmental disorders.

References

Akter, S., Akhter, H., Chaudhury, H. S., Rahman, M. H., Gorski, A., Hasan, M. N., Shin, Y., Rahman, M. A., Nguyen, M. N., et al. (2022). Dietary carbohydrates: Pathogenesis and potential therapeutic targets to obesity-associated metabolic syndrome. BioFactors, 48(5), 750–762. https://doi.org/10.1002/biof.1886

American Council on Exercise. (2009). Body Fat Percentage. ACE Fitness

Arroyo-Jousse, V., Jaramillo, A., Castaño-Moreno, E., Lépez, M., Carrasco-Negüe, K., & Casanello, P. (2020). Adipokines underlie the early origins of obesity and associated metabolic comorbidities in the offspring of women with pregestational obesity. Biochimica et biophysica acta. Molecular basis of disease, 1866(2), 165558. https://doi.org/10.1016/j.bbadis.2019.165558

Barker, D. J. P. (1990). The fetal and infant origins of adult disease. BMJ, 301(6761), 1111. https://doi.org/10.1136/bmj.301.6761.1111

Barker, D. J. P., Osmond, C., Winter, P. D., Margetts, B., & Simmonds, S. J. (1993). Weight in infancy and death from ischaemic heart disease. The Lancet, 341(8853), 1312-1313. https://doi.org/10.1016/0140-6736(93)90986-9

Baloyi, S.M., & Mokwena, K. (2021). Metabolic Syndrome in Reproductive Health: Urgent Call for Screening. IntechOpen. doi: 10.5772/intechopen.95971).

Bersain, R., Mishra, D., Juneja, M., et al. (2023). Comparison of Neurodevelopmental Status in Early Infancy of Infants of Women With and Without Gestational Diabetes Mellitus. Indian Journal of Pediatrics, 90, 1083–1088. https://doi.org/10.1007/s12098-023-04639-0

Bhatti, G. K., Bhadada, S. K., Vijayvergiya, R., Mastana, S. S., & Bhatti, J. S. (2016). Metabolic syndrome and risk of major coronary events among the urban diabetic patients: North Indian Diabetes and Cardiovascular Disease Study-NIDCVD-2. Journal of diabetes and its complications, 30(1), 72–78. https://doi.org/10.1016/j.jdiacomp.2015.07.008

Boney, C. M., Verma, A., Tucker, R., & Vohr, B. R. (2005). Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics, 115(3), e290-e296.

Carter, S. A., Lin, J. C., Chow, T., Yu, X., Rahman, M. M., Martinez, M. P., Feldman, K., Eckel, S. P., Chen, J.-C., Chen, Z., Levitt, P., Lurmann, F. W., McConnell, R., & Xiang, A. H. (2023). Maternal obesity, diabetes, preeclampsia, and asthma during pregnancy and likelihood of autism spectrum disorder with gastrointestinal disturbances in offspring. Autism, 27(4), 916-926. https://doi.org/10.1177/13623613221118430

Clemente-Suárez, V. J., Beltrán-Velasco, A. I., Redondo-Flórez, L., Martín-Rodríguez, A., & Tornero-Aguilera, J. F. (2023). Global Impacts of Western Diet and Its Effects on Metabolism and Health: A Narrative Review. Nutrients, 15(12), 2749. https://doi.org/10.3390/nu15122749

Del Prato S. (2009). Role of glucotoxicity and lipotoxicity in the pathophysiology of Type 2 diabetes mellitus and emerging treatment strategies. Diabetic medicine : a journal of the British Diabetic Association, 26(12), 1185–1192. https://doi.org/10.1111/j.1464-5491.2009.02847.x

de Sousa, R. A. L., de Lima, E. V., da Silva, T. P., de Souza, R. V., Figueiredo, C. P., Passos, G. F., & Clarke, J. R. (2019). Late Cognitive Consequences of Gestational Diabetes to the Offspring, in a New Mouse Model. Molecular neurobiology, 56(11), 7754–7764. https://doi.org/10.1007/s12035-019-1624-0

Dobrowolski, P., Prejbisz, A., Kuryłowicz, A., Baska, A., Burchardt, P., Chlebus, K. ... Bogdański, P. (2022). Metabolic syndrome – a new definition and management guidelines. A joint position paper by the Polish Society of Hypertension, Polish Society for the Treatment of Obesity, Polish Lipid Association, Polish Association for Study of Liver, Polish Society of Family Medicine, Polish Society of Lifestyle Medicine, Division of Prevention and Epidemiology Polish Cardiac Society, “Club 30” Polish Cardiac Society, and Division of Metabolic and Bariatric Surgery Society of Polish Surgeons. Archives of Medical Science, 18(5), 1133-1156. https://doi.org/10.5114/aoms/152921

Engin A. B. (2017). What Is Lipotoxicity? Advances in experimental medicine and biology, 960, 197–220. https://doi.org/10.1007/978-3-319-48382-5_8

Fuchs, F., Senat, M. V., Rey, E., Balayla, J., Chaillet, N., Bouyer, J., & Audibert, F. (2017). Impact of maternal obesity on the incidence of pregnancy complications in France and Canada. Scientific reports, 7(1), 10859. https://doi.org/10.1038/s41598-017-11432-5

Gleason, J. L., Shenassa, E. D., & Thoma, M. E. (2019). Self-reported infertility, metabolic dysfunction, and cardiovascular events: a cross-sectional analysis among U.S. women. Fertility and sterility, 111(1), 138–146. https://doi.org/10.1016/j.fertnstert.2018.10.009

Graham, C. A.-M., Pipe, J., Holton, J., Tamba, K., Lorente-Cebrián, S., González-Muniesa, P., & Mavrommatis, Y. (2019). Associations Between Genetic Predisposition, Fat Taste and Obesity. Proceedings of the Nutrition Society, 78(OCE1). doi: 10.1017/s0029665119000065

Grieger, J. A., Grzeskowiak, L. E., Smithers, L. G., Bianco-Miotto, T., Leemaqz, S. Y., Andraweera, P., Poston, L., McCowan, L. M., Kenny, L. C., Myers, J., Walker, J. J., Norman, R. J., Dekker, G. A., & Roberts, C. T. (2019). Metabolic syndrome and time to pregnancy: a retrospective study of nulliparous women. BJOG : an international journal of obstetrics and gynaecology, 126(7), 852–862. https://doi.org/10.1111/1471-0528.15647

Guo, D., Ju, R., Dai, J., & Zhang, H. (2025). Autism spectrum disorders in offspring exposed to maternal gestational diabetes: A meta-analysis and systematic review. Review Journal of Autism and Developmental Disorders, 12(1), 69–79. https://doi.org/10.1007/s40489-023-00380-8

Hadžiabdić, O.M. (2015). Metabolički sindrom. Medicus, 24, 191-203.

Hampl, S. E., Hassink, S. G., Skinner, A. C., Armstrong, S. C., Barlow, S. E., Bolling, C. F., Avila Edwards, K. C., Eneli, I., Hamre, R., Joseph, M. M., Lunsford, D., Mendonca, E., Michalsky, M. P., Mirza, N., Ochoa, E. R., Jr, Sharifi, M., Staiano, A. E., Weedn, A. E., Flinn, S. K., Lindros, J., & Okechukwu, K. (2023). Clinical practice guideline for the evaluation and treatment of children and adolescents with obesity. Pediatrics, 151(2), e2022060640. https://doi.org/10.1542/peds.2022-060640

Horvath, B., Bodecs, T., Boncz, I., & Bodis, J. (2013). Metabolic syndrome in normal and complicated pregnancies. Metabolic syndrome and related disorders, 11(3), 185–188. https://doi.org/10.1089/met.2012.0086

Houshmand, A., Jensen, D. M., Mathiesen, E. R., & Damm, P. (2013). Evolution of diagnostic criteria for gestational diabetes mellitus. Acta obstetricia et gynecologica Scandinavica, 92(7), 739–745. https://doi.org/10.1111/aogs.12152

Jones, A. D., Zhao, G., Jiang, Y. P., Zhou, M., Xu, G., Kaciroti, N., Zhang, Z., & Lozoff, B. (2016). Maternal obesity during pregnancy is negatively associated with maternal and neonatal iron status. European journal of clinical nutrition, 70(8), 918–924. https://doi.org/10.1038/ejcn.2015.229

Koren, R., Hochman, Y., Koren, S., Ziv-Baran, T., & Wiener, Y. (2019). Effect of pre-gestational weight and gestational weight gain in women with gestational diabetes controlled with medication on pregnancy outcomes - is recommended weight gain too liberal?. Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology, 35(4), 328–331. https://doi.org/10.1080/09513590.2018.1525701

Krakowiak, P., Walker, C. K., Bremer, A. A., Baker, A. S., Ozonoff, S., Hansen, R. L., & Hertz-Picciotto, I. (2012). Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics, 129(5), e1121–e1128. https://doi.org/10.1542/peds.2011-2583

Łakoma, K., Kukharuk, O., & Śliż, D. (2023). The Influence of Metabolic Factors and Diet on Fertility. Nutrients, 15(5), 1180. https://doi.org/10.3390/nu15051180

Lazar M. A. (2005). How obesity causes diabetes: not a tall tale. Science (New York, N.Y.), 307(5708), 373–375. https://doi.org/10.1126/science.1104342

Li, M., Fallin, M. D., Riley, A., Landa, R., Walker, S. O., Silverstein, M., Caruso, D., Pearson, C., Kiang, S., Dahm, J. L., Hong, X., Wang, G., Wang, M. C., Zuckerman, B., & Wang, X. (2016). The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities. Pediatrics, 137(2), e20152206. https://doi.org/10.1542/peds.2015-2206

Li, R., Wu, J., He, J., Wang, Y., Liu, X., Chen, X., Tong, C., Ding, Y., Su, Y., Chen, W., Zhang, C., & Gao, R. (2017). Mice endometrium receptivity in early pregnancy is impaired by maternal hyperinsulinemia. Molecular medicine reports, 15(5), 2503–2510. https://doi.org/10.3892/mmr.2017.6322

Li, S. W., Yu, H. R., Sheen, J. M., Tiao, M. M., Tain, Y. L., Lin, I. C., Lin, Y. J., Chang, K. A., Tsai, C. C., & Huang, L. T. (2017). A maternal high-fat diet during pregnancy and lactation, in addition to a postnatal high-fat diet, leads to metabolic syndrome with spatial learning and memory deficits: beneficial effects of resveratrol. Oncotarget, 8(67), 111998–112013. https://doi.org/10.18632/oncotarget.22960

Lima, Maria do Carmo Pinto, Melo, Adriana Suely Oliveira, Sena, Aline Silva Santos, Barros, Vivianne de Oliveira, & Amorim, Melania Maria Ramos. (2019). Metabolic syndrome in pregnancy and postpartum: prevalence and associated factors. Revista da Associação Médica Brasileira, 65(12), 1489-1495. https://doi.org/10.1590/1806-9282.65.12.1489

Lin, J., Gu, W., & Huang, H. (2022). Effects of Paternal Obesity on Fetal Development and Pregnancy Complications: A Prospective Clinical Cohort Study. Frontiers in endocrinology, 13, 826665. https://doi.org/10.3389/fendo.2022.826665

Loche, E., Blackmore, H. L., Carpenter, A. A., Beeson, J. H., Pinnock, A., Ashmore, T. J., Aiken, C. E., de Almeida-Faria, J., Schoonejans, J. M., Giussani, D. A., Fernandez-Twinn, D. S., & Ozanne, S. E. (2018). Maternal diet-induced obesity programmes cardiac dysfunction in male mice independently of post-weaning diet. Cardiovascular research, 114(10), 1372–1384. https://doi.org/10.1093/cvr/cvy082

Luo, S. S., Zou, K. X., Zhu, H., Cheng, Y., Yan, Y. S., Sheng, J. Z., Huang, H. F., & Ding, G. L. (2022). Integrated Multi-Omics Analysis Reveals the Effect of Maternal Gestational Diabetes on Fetal Mouse Hippocampi. Frontiers in Cell and Developmental Biology, 10, 748862. https://doi.org/10.3389/fcell.2022.748862

Matias, S. L., Pearl, M., Lyall, K., Croen, L. A., Kral, T. V. E., Fallin, D., Lee, L.-C., Bradley, C. B., Schieve, L. A., & Windham, G. C. (2021). Maternal prepregnancy weight and gestational weight gain in association with autism and developmental disorders in offspring. Obesity, 29(10), 1623-1630. https://doi.org/10.1002/oby.23228

Melnik, B. C., John, S. M., & Schmitz, G. (2011). Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from laron syndrome. Nutrition & metabolism, 8, 41. https://doi.org/10.1186/1743-7075-8-41

Mottola, M. F., & Artal, R. (2016). Fetal and maternal metabolic responses to exercise during pregnancy. Early human development, 94, 33–41. https://doi.org/10.1016/j.earlhumdev.2016.01.008

National Heart, Lung, and Blood Institute. (2020). The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. https://www.nhlbi.nih.gov/files/docs/guidelines/prctgd_c.pdf

National Institute of Diabetes and Digestive and Kidney Diseases. (2021). Health Risks of Overweight and Obesity. https://www.niddk.nih.gov/health-information/weight-management/adult-overweight-obesity/health-risks

Ristic-Medic, D., Vucic, V. (2013) Dietary Fats and Metabolic Syndrome. Journal of Nutrition Health Food Science 1(1), 8. http://dx.doi.org/10.15226/jnhfs.2013.00105

Rojas-Rodriguez, R., Lifshitz, L. M., Bellve, K. D., Min, S. Y., Pires, J., Leung, K., … Rojas-Rodriguez, R., Lifshitz, L. M., Bellve, K. D., Min, S. Y., Pires, J., Leung, K., Boeras, C., Sert, A., Draper, J. T., Corvera, S., & Moore Simas, T. A. (2015). Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus. Diabetologia, 58(9), 2106–2114. https://doi.org/10.1007/s00125-015-3662-0

Ryznar, R. J., Phibbs, L., & Van Winkle, L. J. (2021). Epigenetic modifications at the center of the Barker hypothesis and their transgenerational implications. International Journal of Environmental Research and Public Health, 18(23), 12728. https://doi.org/10.3390/ijerph182312728

Sarker, G., & Peleg-Raibstein, D. (2018). Maternal Overnutrition Induces Long-Term Cognitive Deficits across Several Generations. Nutrients, 11(1), 7. https://doi.org/10.3390/nu11010007 Selovic, A., Sarac, J., & Missoni, S. (2015). Changes in adipose tissue distribution during pregnancy estimated by ultrasonography. The Journal of Maternal-Fetal & Neonatal Medicine, 29(13), 2131–2137. doi: 10.3109/14767058.2015.1077220

Serazin, V., Duval, F., Wainer, R., Ravel, C., Vialard, F., Molina-Gomes, D., Dieudonne, M. N., & Dos Santos, E. (2018). Are leptin and adiponectin involved in recurrent pregnancy loss?. The journal of obstetrics and gynaecology research, 44(6), 1015–1022. https://doi.org/10.1111/jog.13623

Shapiro, A.L.B., Ringham, B.M., Glueck, D.H., Norris, J.M., Barbour, L.A., Friedman, J.E., & Dabelea, D. (2017). Infant adiposity is independently associated with a maternal high fat diet but not related to niacin intake: The Healthy Start Study. Maternal and Child Health Journal, 21(8), 1662–1668. https://doi.org/10.1007/s10995-016-2258-8

Sharp, G.C., & Lawlor, D.A. (2019). Paternal impact on the life course development of obesity and type 2 diabetes in the offspring. Diabetologia, 62(10), 1802–1810. https://doi.org/10.1007/s00125-019-4919-9

Sigit, F. S., Tahapary, D. L., Trompet, S., Sartono, E., Willems van Dijk, K., Rosendaal, F. R., & de Mutsert, R. (2020). The prevalence of metabolic syndrome and its association with body fat distribution in middle-aged individuals from Indonesia and the Netherlands: a cross-sectional analysis of two population-based studies. Diabetology & metabolic syndrome, 12, 2. https://doi.org/10.1186/s13098-019-0503-1

Stubert, J., Reister, F., Hartmann, S., & Janni, W. (2018). The Risks Associated With Obesity in Pregnancy. Deutsches Arzteblatt international, 115(16), 276–283. https://doi.org/10.3238/arztebl.2018.0276

Surén, P., Gunnes, N., Roth, C., Bresnahan, M., Hornig, M., Hirtz, D., Lie, K. K., Lipkin, W. I., Magnus, P., Reichborn-Kjennerud, T., Schjølberg, S., Susser, E., Oyen, A. S., Smith, G. D., & Stoltenberg, C. (2014). Parental obesity and risk of autism spectrum disorder. Pediatrics, 133(5), e1128–e1138. https://doi.org/10.1542/peds.2013-3664

Sweeting, A., Wong, J., Murphy, H. R., & Ross, G. P. (2022). A clinical update on gestational diabetes mellitus. Endocrine Reviews, 43(5), 763-793. https://doi.org/10.1210/endrev/bnac003

Tang, J., Xu, Y., Wang, Z., et al. (2023). Association between metabolic healthy obesity and female infertility: the national health and nutrition examination survey, 2013–2020. BMC Public Health, 23, 1524. https://doi.org/10.1186/s12889-023-16397-x

Teegarden, S. L., Scott, A. N., & Bale, T. L. (2009). Early life exposure to a high fat diet promotes long-term changes in dietary preferences and central reward signaling. Neuroscience, 162(4),924–932. https://doi.org/10.1016/j.neuroscience.2009.05.029

van der Klaauw, A. A., & Farooqi, I. S. (2015). The hunger genes: pathways to obesity. Cell, 161(1), 119–132. https://doi.org/10.1016/j.cell.2015.03.008

Veselinović, A., Petrović, S., Žikić, V., Subotić, M., Jakovljević, V., Jeremić, N., & Vučić, V. (2021). Neuroinflammation in Autism and Supplementation Based on Omega-3 Polyunsaturated Fatty Acids: A Narrative Review. Medicina (Kaunas, Lithuania), 57(9), 893. https://doi.org/10.3390/medicina57090893

Voerman, E., Santos, S., Patro Golab, B., Amiano, P., Ballester, F., Barros, H., Bergström, A., Charles, M. A., Chatzi, L., Chevrier, C., Chrousos, G. P., Corpeleijn, E., Costet, N., Crozier, S., Devereux, G., Eggesbø, M., Ekström, S., Fantini, M. P., Farchi, S., Forastiere, F., … Jaddoe, V. W. V. (2019). Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis. PLoS medicine, 16(2), e1002744. https://doi.org/10.1371/journal.pmed.1002744

Wang, H., Li, N., Chivese, T., Werfalli, M., Sun, H., Yuen, L., Hoegfeldt, C. A., Elise Powe, C., Immanuel, J., Karuranga, S., Divakar, H., Levitt, N., Li, C., Simmons, D., & Yang, X.; IDF Diabetes Atlas Committee Hyperglycaemia in Pregnancy Special Interest Group. (2022). IDF Diabetes Atlas: Estimation of global and regional gestational diabetes mellitus prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group's criteria. Diabetes Research and Clinical Practice, 183, 109050. https://doi.org/10.1016/j.diabres.2021.109050

World Health Organization. (2024). Infertility. Retrieved from https://www.who.int/news-room/fact-sheets/detail/infertility

World Health organization (2000). Obesity: preventing and managing the global epidemic. Report of a WHO consultation. (2000). World Health Organization technical report series, 894, i–253. https://iris.who.int/handle/10665/42330

Yu, Z., Han, S., Zhu, J., Sun, X., Ji, C., & Guo, X. (2013). Pre-pregnancy body mass index in relation to infant birth weight and offspring overweight/obesity: a systematic review and meta-analysis. PloS one, 8(4), e61627. https://doi.org/10.1371/journal.pone.0061627

Zhang, S., Lin, T., Zhang, Y., Liu, X., & Huang, H. (2022). Effects of parental overweight and obesity on offspring’s mental health: A meta-analysis of observational studies. PLoS ONE, 17(12), e0276469. https://doi.org/10.1371/journal.pone.0276469

Published
2025/10/02
Section
Review Paper