Article

Prenatal Environment and Perinatal Factors Associated with Autism Spectrum Disorder

Jianjun Ou1,2,3, Yidong Shen1, Yamin Li 4, Guanglei Xun5, Huaqing Liu6, Yiqun He7, Hui Guo3, Renrong Wu1, Claude Hughes8, Kun Xia3, Jingping Zhao1, Fengyu Zhang1,2,6

1 Department of Psychiatry & Mental Health Institute of the Second Xiangya Hospital, Central South University; The China National Clinical Research Center for Mental Health Disorders; National Technology Institute of Psychiatry; Key Laboratory of Psychiatry and Mental Health of Hunan Province, Changsha, Hunan, China.

2 Global Clinical and Translational Research Institute, Bethesda, Maryland, USA.

3 Center for Medical Genetics and School of Life Sciences, Central South University, Changsha, Hunan, China.

4 Clinical Nursing Teaching and Research Section, the Second Xiangya Hospital, Central South University, Hunan, China.

5 Shandong Mental Health Center, Jinan, Shandong, China.

6 Peking University Clinical Medical School and Beijing Huilongguan Hospital, Changping District, Beijing, China.

7 The First Department of Clinical Psychosomatic Medicine of the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China.

8 Therapeutic Science and Strategy Unit, IQVIA, Research Triangle Park, NC; Department of Obstetrics and Gynecology, Duke University Medical Center. Morrisville, NC, USA.

Received March 19, 2019; Accepted July 31, 2019

ABSTRACT

Background: Both genetic and epidemiological studies have indicated that environmental factors play an essential role in the development of autism spectrum disorder (ASD). We conducted this study to identify maternal exposure to environmental factors, in particular during the fetal development or perinatal period, associated with ASD.

Methods: Two independent samples of children with ASD and typical developed (TD) were from distinct regions in China. Multiple logistic regression analysis was performed to identify factors associated with ASD in each sample and then in the combined sample.

Results: Five factors were consistently associated with ASD in both samples. In the combined sample, maternal chemical exposure (odds ratio [OR] =4.50; 95% CI: 2.38-8.52), use of medication (OR = 3.19; 95% CI: 2.19-4.65), maternal infection (OR = 2.68; 95% CI: 1.99-3.61), threatened abortion (OR = 2.37; 95% CI: 1.61-3.50), and induced abortion before having the child (OR = 2.07; 95% CI: 1.65-2.60) showed strong associations with ASD; moreover, five factors explained 10-15% of the variation in the risk of ASD. A significant interaction between maternal infection and the use of medication during pregnancy was consistently detected in both independent and combined samples together.

Conclusion: Two novel risk factors of maternal chemical exposure and induced abortion may have important implications for understanding the etiology of ASD, particularly in China. Prospective studies are needed to validate these findings, and necessary interventions are recommended to reduce the risk of ASD.

KEYWORDS

Autism spectrum disorder, chemical exposure, induced abortion, maternal infection

Copyright © 2019 by the author(s). Licensee Global Clinical and Translational Research Institute, Bethesda, MD. This is an open-access article distributed under the terms and conditions of the Creative Commons Attribution License (CCBY4.0, https://creative-commons.org /licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium provided the original work is properly cited.

How to cite this article:

Ou, J, Shen Y, Li Y, Xun G, Liu H, He Y, Guo H, Wu R, Hughes C, Xia K, Zhao J, Zhang F. Prenatal Environment and Perinatal Factors Associated with Autism Spectrum Disorder. Glob Clin Transl Res. 2019; 1(3): 100-108. doi:10.36316/gcatr.01.0015

References

1.      Lai MC, Lombardo MV, Baron-Cohen S. Autism. Lancet. 2014;383(9920):896-910.

2.      Ou JJ, Shi LJ, Xun GL, Chen C, Wu RR, Luo XR, et al. Employment and financial burden of families with preschool children diagnosed with autism spectrum disorders in urban China: results from a descriptive study. BMC Psychiatry. 2015;15:3.

3.      Wang Y, Xiao L, Chen RS, Chen C, Xun GL, Lu XZ, et al. Social impairment of children with autism spectrum disorder affects the parental quality of life in different ways. Psychiat Res. 2018;266:168-74.

4.      Xia K, Guo H, Hu Z, Xun G, Zuo L, Peng Y, et al. Common genetic variants on 1p13.2 associate with risk of autism. Mol Psychiatry. 2014;19(11):1212-9.

5.      Wang K, Zhang H, Ma D, Bucan M, Glessner JT, Abrahams BS, et al. Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature. 2009;459(7246):528-33.

6.      Anney R, Klei L, Pinto D, Regan R, Conroy J, Magalhaes TR, et al. A genome-wide scan for common alleles affecting risk for autism. Hum Mol Genet. 2010;19(20):4072-82.

7.      Gaugler T, Klei L, Sanders SJ, Bodea CA, Goldberg AP, Lee AB, et al. Most genetic risk for autism resides with common variation. Nat Genet. 2014;46(8):881-5.

8.      Wang T, Guo H, Xiong B, Stessman HA, Wu H, Coe BP, et al. De novo genic mutations among a Chinese autism spectrum disorder cohort. Nat Commun. 2016;7:13316.

9.      Stessman HA, Xiong B, Coe BP, Wang T, Hoekzema K, Fenckova M, et al. Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nat Genet. 2017;49(4):515-26.

10.   Bilder D, Pinborough-Zimmerman J, Miller J, McMahon W. Prenatal, perinatal, and neonatal factors associated with autism spectrum disorders. Pediatrics. 2009;123(5):1293-300.

11.   Jiang HY, Xu LL, Shao L, Xia RM, Yu ZH, Ling ZX, et al. Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis. Brain Behav Immun. 2016;58:165-72.

12.   Shen YD, Dong HX, Lu XZ, Lian N, Xun GL, Shi LJ, et al. Associations among maternal pre-pregnancy body mass index, gestational weight gain, and risk of autism in the Han Chinese population. Bmc Psychiatry. 2018;18.

13.   Curran EA, Dalman C, Kearney PM, Kenny LC, Cryan JF, Dinan TG, et al. Association Between Obstetric Mode of Delivery and Autism Spectrum Disorder: A Population-Based Sibling Design Study. JAMA Psychiatry. 2015;72(9):935-42.

14.   Li J, Vestergaard M, Obel C, Christensen J, Precht DH, Lu M, et al. A nationwide study on the risk of autism after prenatal stress exposure to maternal bereavement. Pediatrics. 2009;123(4):1102-7.

15.   Atladottir HO, Thorsen P, Ostergaard L, Schendel DE, Lemcke S, Abdallah M, et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. Journal of autism and developmental disorders. 2010;40(12):1423-30.

16.   Patterson PH. Maternal infection and immune involvement in autism. Trends Mol Med. 2011;17(7):389-94.

17.   Nachman RM, Mao G, Zhang X, Hong X, Chen Z, Soria CS, et al. Intrauterine Inflammation and Maternal Exposure to Ambient PM2.5 during Preconception and Specific Periods of Pregnancy: The Boston Birth Cohort. Environ Health Perspect. 2016;124(10):1608-15.

18.   Deng Q, Lu C, Jiang W, Zhao J, Deng L, Xiang Y. Association of outdoor air pollution and indoor renovation with an early childhood ear infection in China. Chemosphere. 2017;169:288-96.

19.   Shen Y, Xun G, Guo H, He Y, Ou J, Dong H, et al. Association and gene-gene interactions study of reelin signaling pathway-related genes with autism in the Han Chinese population. Autism Res. 2016;9(4):436-42.

20.   Chen C, Shen YD, Xun GL, Cai WX, Shi LJ, Xiao L, et al. Aggressive behaviors and treatable risk factors of preschool children with autism spectrum disorder. Autism Research. 2017;10(6):1155-62.

21.   International Schizophrenia C, Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, et al. Common polygenic variation contributes to the risk of schizophrenia and bipolar disorder. Nature. 2009;460(7256):748-52.

22.   Kinney DK, Munir KM, Crowley DJ, Miller AM. Prenatal stress and risk for autism. Neuroscience and biobehavioral reviews. 2008;32(8):1519-32.

23.   Lyall K, Croen L, Daniels J, Fallin MD, Ladd-Acosta C, Lee BK, et al. The Changing Epidemiology of Autism Spectrum Disorders. Annu Rev Public Health. 2017;38:81-102.

24.   Costa LG, Chang YC, Cole TB. Developmental Neurotoxicity of Traffic-Related Air Pollution: Focus on Autism. Curr Environ Health Rep. 2017;4(2):156-65.

25.   Lucchini RG, Dorman DC, Elder A, Veronesi B. Neurological impacts from inhalation of pollutants and the nose-brain connection. Neurotoxicology. 2012;33(4):838-41.

26.   Mohan Kumar SM, Campbell A, Block M, Veronesi B. Particulate matter, oxidative stress, and neurotoxicity. Neurotoxicology. 2008;29(3):479-88.

27.   Li N, Sioutas C, Cho A, Schmitz D, Misra C, Sempf J, et al. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environ Health Perspect. 2003;111(4):455-60.

28.   Wei H, Feng Y, Liang F, Cheng W, Wu X, Zhou R, et al. Role of oxidative stress and DNA hydroxymethylation in the neurotoxicity of fine particulate matter. Toxicology. 2017;380:94-103.

29.   Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. Traffic-related air pollution, particulate matter, and autism. JAMA Psychiatry. 2013;70(1):71-7.

30.   Becerra TA, Wilhelm M, Olsen J, Cockburn M, Ritz B. Ambient air pollution and autism in Los Angeles County, California. Environmental health perspectives. 2013;121(3):380-6.

31.   Jung CR, Lin YT, Hwang BF. Air pollution and newly diagnostic autism spectrum disorders: a population-based cohort study in Taiwan. PloS one. 2013;8(9):e75510.

32.   Gong T, Dalman C, Wicks S, Dal H, Magnusson C, Lundholm C, et al. Perinatal Exposure to Traffic-Related Air Pollution and Autism Spectrum Disorders. Environ Health Perspect. 2017;125(1):119-26.

33.   Brown AS, Derkits EJ. Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. The American journal of psychiatry. 2010;167(3):261-80.

34.   Brown AS, Begg MD, Gravenstein S, Schaefer CA, Wyatt RJ, Bresnahan M, et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Archives of general psychiatry. 2004;61(8):774-80.

35.   Atladottir HO, Henriksen TB, Schendel DE, Parner ET. Autism after infection, febrile episodes, and antibiotic use during pregnancy: an exploratory study. Pediatrics. 2012;130(6):e1447-54.

36.   Shi L, Fatemi SH, Sidwell RW, Patterson PH. Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2003;23(1):297-302.

37.   Manev R, Manev H. Aminoglycoside antibiotics and autism: a speculative hypothesis. BMC psychiatry. 2001;1:5.

38.   Hultman CM, Sparen P, Cnattingius S. Perinatal risk factors for infantile autism. Epidemiology. 2002;13(4):417-23.

39.   Zeng JZ, Zou GY, Song XQ, Ling L. Contraceptive practices and induced abortions status among internal migrant women in Guangzhou, China: a cross-sectional study. Bmc Public Health. 2015;15.

40.   He H, Ostbye T, Daltveit AK. Reproductive and family planning history, knowledge, and needs: a community survey of low-income women in Beijing, China. BMC Women's Health. 2009;9:23.

41.   Burd L, Severud R, Kerbeshian J, Klug MG. Prenatal and perinatal risk factors for autism. J Perinat Med. 1999;27(6):441-50.

42.   Limperopoulos C. Autism spectrum disorders in survivors of extreme prematurity. Clin Perinatol. 2009;36(4):791-805, vi.

43.   Horvath S, Schreiber CA. Unintended Pregnancy, Induced Abortion, and Mental Health. Curr Psychiatry Rep. 2017;19(11):77.