目的 探讨母亲妊娠糖尿病暴露与子代孤独症谱系障碍（autism spectrum disorder，ASD）发生的关联。 方法 采用病例对照研究方法，招募221例ASD儿童与400例健康儿童纳入研究。采用问卷调查及访谈形式收集儿童一般情况、家庭社会经济学特征、母亲孕产史、母亲孕期疾病暴露等情况，采用多因素logistic回归分析探讨母亲妊娠糖尿病暴露与子代ASD发生的关联，并探讨子代性别和妊娠糖尿病暴露对子代ASD的发生是否存在交互作用。 结果 ASD组母亲妊娠糖尿病患病比例显著高于对照组（16.3% vs 9.4%，P=0.014）。校正性别、胎龄情况、出生方式、产次、母亲文化程度等变量后，母亲妊娠糖尿病暴露是子代ASD发生的危险因素（OR=2.18，95%CI：1.04~4.54，P=0.038）；在校正以上变量的基础上，进一步校正孕早期复合维生素服用、孕前3个月叶酸服用和辅助生殖等变量后，结果趋势未发生改变，但未见统计学意义（OR=1.94，95%CI：0.74~5.11，P=0.183）。妊娠糖尿病暴露与子代性别对子代ASD的发生存在交互作用（P<0.001）；性别分层分析显示，仅在妊娠糖尿病母亲的男性子代中ASD发病风险显著增加（OR=3.67，95%CI：1.16~11.65，P=0.027）。 结论 母亲妊娠糖尿病暴露可能增加子代ASD的发生风险；妊娠糖尿病暴露和子代性别对子代ASD的发生存在交互作用。
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.
关键词
孤独症谱系障碍 /
妊娠糖尿病 /
性别交互 /
风险 /
病例-对照研究 /
儿童
Key words
Autism spectrum disorder /
Gestational diabetes mellitus /
Sex interaction /
Risk /
Case-control study /
Child
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
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.
基金
广州市科技计划项目（202102010232）。
PDF(553 KB)
