Association between maternal gestational diabetes mellitus and the risk of autism spectrum disorder in offspring

LIU Xian, GUO Cheng, ZOU Ming-Yang, FENG Fang-Mei, LIANG Si-Min, CHEN Wen-Xiong, WU Li-Jie

Chinese Journal of Contemporary Pediatrics ›› 2023, Vol. 25 ›› Issue (8) : 818-823.

PDF(553 KB)
PDF(553 KB)
Chinese Journal of Contemporary Pediatrics ›› 2023, Vol. 25 ›› Issue (8) : 818-823. DOI: 10.7499/j.issn.1008-8830.2301021
CLINICAL RESEARCH

Association between maternal gestational diabetes mellitus and the risk of autism spectrum disorder in offspring

  • LIU Xian1,2, GUO Cheng3, ZOU Ming-Yang1, FENG Fang-Mei3, LIANG Si-Min3, CHEN Wen-Xiong3,4, WU Li-Jie1
Author information +
History +

Abstract

Objective To explore the association between maternal gestational diabetes mellitus (GDM) exposure and the development of autism spectrum disorder (ASD) in offspring. Methods A case-control study was conducted, recruiting 221 children with ASD and 400 healthy children as controls. Questionnaires and interviews were used to collect information on general characteristics of the children, socio-economic characteristics of the family, maternal pregnancy history, and maternal disease exposure during pregnancy. Multivariate logistic regression analysis was used to investigate the association between maternal GDM exposure and the development of ASD in offspring. The potential interaction between offspring gender and maternal GDM exposure on the development of ASD in offspring was explored. Results The proportion of maternal GDM was significantly higher in the ASD group compared to the control group (16.3% vs 9.4%, P=0.014). After adjusting for variables such as gender, gestational age, mode of delivery, parity, and maternal education level, maternal GDM exposure was a risk factor for ASD in offspring (OR=2.18, 95%CI: 1.04-4.54, P=0.038). On the basis of adjusting the above variables, after further adjusting the variables including prenatal intake of multivitamins, folic acid intake in the first three months of pregnancy, and assisted reproduction the result trend did not change, but no statistical significance was observed (OR=1.94, 95%CI: 0.74-5.11, P=0.183). There was an interaction between maternal GDM exposure and offspring gender on the development of ASD in offspring (P<0.001). Gender stratified analysis showed that only in male offspring of mothers with GDM, the risk of ASD was significantly increased (OR=3.67, 95%CI: 1.16-11.65, P=0.027). Conclusions Maternal GDM exposure might increase the risk of ASD in offspring. There is an interaction between GDM exposure and offspring gender in the development of ASD in offspring.

Key words

Autism spectrum disorder / Gestational diabetes mellitus / Sex interaction / Risk / Case-control study / Child

Cite this article

Download Citations
LIU Xian, GUO Cheng, ZOU Ming-Yang, FENG Fang-Mei, LIANG Si-Min, CHEN Wen-Xiong, WU Li-Jie. Association between maternal gestational diabetes mellitus and the risk of autism spectrum disorder in offspring[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(8): 818-823 https://doi.org/10.7499/j.issn.1008-8830.2301021

References

1 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders[M]. 5th ed. Arlington, VA: American Psychiatric Association, 2013.
2 Maenner MJ, Shaw KA, Bakian AV, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years: autism and developmental disabilities monitoring network, 11 sites, United States, 2018[J]. MMWR Surveill Summ, 2021, 70(11): 1-16. PMID: 34855725. PMCID: PMC8639024. DOI: 10.15585/mmwr.ss7011a1.
3 Zhou H, Xu X, Yan W, et al. Prevalence of autism spectrum disorder in China: a nationwide multi-center population-based study among children aged 6 to 12 years[J]. Neurosci Bull, 2020, 36(9): 961-971. PMID: 32607739. PMCID: PMC7475160. DOI: 10.1007/s12264-020-00530-6.
4 Li YA, Chen ZJ, Li XD, et al. Epidemiology of autism spectrum disorders: global burden of disease 2019 and bibliometric analysis of risk factors[J]. Front Pediatr, 2022, 10: 972809. PMID: 36545666. PMCID: PMC9760802. DOI: 10.3389/fped.2022.972809.
5 Qiu X, Lu JH, He JR, et al. The born in Guangzhou cohort study (BIGCS)[J]. Eur J Epidemiol, 2017, 32(4): 337-346. PMID: 28321694. DOI: 10.1007/s10654-017-0239-x.
6 Mistry SK, Das Gupta R, Alam S, et al. Gestational diabetes mellitus (GDM) and adverse pregnancy outcome in South Asia: a systematic review[J]. Endocrinol Diabetes Metab, 2021, 4(4): e00285. PMID: 34505412. PMCID: PMC8502223. DOI: 10.1002/edm2.285.
7 Thirumoorthy C, Deepa M, Srikumar BN, et al. Altered levels of neurobiological biomarkers at the interface of depression and gestational diabetes mellitus in Asian Indian women[J]. Neuropeptides, 2022, 93: 102245. PMID: 35461022. DOI: 10.1016/j.npep.2022.102245.
8 Cheroni C, Caporale N, Testa G. Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology[J]. Mol Autism, 2020, 11(1): 69. PMID: 32912338. PMCID: PMC7488083. DOI: 10.1186/s13229-020-00370-1.
9 Chen S, Zhao S, Dalman C, et al. Association of maternal diabetes with neurodevelopmental disorders: autism spectrum disorders, attention-deficit/hyperactivity disorder and intellectual disability[J]. Int J Epidemiol, 2021, 50(2): 459-474. PMID: 33221916. PMCID: PMC8128461. DOI: 10.1093/ije/dyaa212.
10 Xiang AH. Association of maternal diabetes with autism in offspring[J]. JAMA, 2017, 317(5): 537-538. PMID: 28170476. DOI: 10.1001/jama.2016.20122.
11 Ferri SL, Abel T, Brodkin ES. Sex differences in autism spectrum disorder: a review[J]. Curr Psychiatry Rep, 2018, 20(2): 9. PMID: 29504047. PMCID: PMC6477922. DOI: 10.1007/s11920-018-0874-2.
12 Wang H, Li N, Chivese T, et al. 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[J]. Diabetes Res Clin Pract, 2022, 183: 109050. PMID: 34883186. DOI: 10.1016/j.diabres.2021.109050.
13 Connolly N, Anixt J, Manning P, et al. Maternal metabolic risk factors for autism spectrum disorder: an analysis of electronic medical records and linked birth data[J]. Autism Res, 2016, 9(8): 829-837. PMID: 26824581. DOI: 10.1002/aur.1586.
14 吕亚奇, 冯国双. 医学研究中常见的样本量估算方法[J]. 慢性病学杂志, 2016, 17(4): 359-361. DOI: 10.16440/j.cnki.1674-8166.2016.04.001
15 Leonard H, de Klerk N, Bourke J, et al. Maternal health in pregnancy and intellectual disability in the offspring: a population-based study[J]. Ann Epidemiol, 2006, 16(6): 448-454. PMID: 16182562. DOI: 10.1016/j.annepidem.2005.05.002.
16 Rahman MM, Shu YH, Chow T, et al. Prenatal exposure to air pollution and autism spectrum disorder: sensitive windows of exposure and sex differences[J]. Environ Health Perspect, 2022, 130(1): 17008. PMID: 35040691. PMCID: PMC8765363. DOI: 10.1289/EHP9509.
17 Jo H, Eckel SP, Wang X, et al. Sex-specific associations of autism spectrum disorder with residential air pollution exposure in a large Southern California pregnancy cohort[J]. Environ Pollut, 2019, 254(Pt A): 113010. PMID: 31554142. PMCID: PMC6764604. DOI: 10.1016/j.envpol.2019.113010.
18 Bolton JL, Huff NC, Smith SH, et al. Maternal stress and effects of prenatal air pollution on offspring mental health outcomes in mice[J]. Environ Health Perspect, 2013, 121(9): 1075-1082. PMID: 23823752. PMCID: PMC3764088. DOI: 10.1289/ehp.1306560.
19 Thongkorn S, Kanlayaprasit S, Panjabud P, et al. Sex differences in the effects of prenatal bisphenol A exposure on autism-related genes and their relationships with the hippocampus functions[J]. Sci Rep, 2021, 11(1): 1241. PMID: 33441873. PMCID: PMC7806752. DOI: 10.1038/s41598-020-80390-2.
20 Schaafsma SM, Gagnidze K, Reyes A, et al. Sex-specific gene-environment interactions underlying ASD-like behaviors[J]. Proc Natl Acad Sci U S A, 2017, 114(6): 1383-1388. PMID: 28115688. PMCID: PMC5307430. DOI: 10.1073/pnas.1619312114.
21 Jacquemont S, Coe BP, Hersch M, et al. A higher mutational burden in females supports a "female protective model" in neurodevelopmental disorders[J]. Am J Hum Genet, 2014, 94(3): 415-425. PMID: 24581740. PMCID: PMC3951938. DOI: 10.1016/j.ajhg.2014.02.001.
22 李占魁, 白瑞苗. 妊娠期高血糖暴露对子代神经发育结局的影响[J]. 中国儿童保健杂志, 2022, 30(10): 1045-1048. DOI: 10.11852/zgetbjzz2022-1061.
23 Salinas-Roca B, Rubió-Piqué L, Montull-López A. Polyphenol intake in pregnant women on gestational diabetes risk and neurodevelopmental disorders in offspring: a systematic review[J]. Nutrients, 2022, 14(18): 3753. PMID: 36145129. PMCID: PMC9502213. DOI: 10.3390/nu14183753.
24 Howe CG, Cox B, Fore R, et al. Maternal gestational diabetes mellitus and newborn DNA methylation: findings from the pregnancy and childhood epigenetics consortium[J]. Diabetes Care, 2020, 43(1): 98-105. PMID: 31601636. PMCID: PMC6925578. DOI: 10.2337/dc19-0524.
25 Tylee DS, Sun J, Hess JL, et al. Genetic correlations among psychiatric and immune-related phenotypes based on genome-wide association data[J]. Am J Med Genet B Neuropsychiatr Genet, 2018, 177(7): 641-657. PMID: 30325587. PMCID: PMC6230304. DOI: 10.1002/ajmg.b.32652.
26 Tisato V, Silva JA, Longo G, et al. Genetics and epigenetics of one-carbon metabolism pathway in autism spectrum disorder: a sex-specific brain epigenome?[J]. Genes (Basel), 2021, 12(5): 782. PMID: 34065323. PMCID: PMC8161134. DOI: 10.3390/genes12050782.
PDF(553 KB)

Accesses

Citation

Detail

Sections
Recommended

/