The association of in utero tobacco smoke exposure, quantified by serum cotinine, and Autism Spectrum Disorder
Open accessAbstract
Previous studies on in utero exposure to maternal environmental tobacco smoke (ETS) or maternal active smoking and Autism Spectrum Disorder (ASD) have not been entirely consistent, and no studies have examined in utero cotinine concentrations as an exposure classification method. We measured cotinine in stored second trimester maternal serum for 498 ASD cases and 499 controls born in California in 2011–2012. We also obtained self‐reported maternal cigarette smoking during and immediately prior to pregnancy, as well as covariate data, from birth records. Using unconditional logistic regression, we found no association between log10 cotinine concentrations and odds for developing ASD among children of non‐smokers (aOR: 0.93 [95% CI: 0.69, 1.25] per ng/ml), which represents exposure to ETS, though there may be a possible interaction with race. We found no association between cotinine‐defined smoking (≥3.08 ng/ml vs. <3.08 ng/ml) (adjusted odds ratio [aOR]: 0.73 (95% confidence interval [95% CI]: 0.35, 1.54)) or self‐reported smoking (aOR: 1.64 [95% CI: 0.65, 4.16]) and ASD. In one of the few studies of ETS and the first with measured cotinine, our results indicate no overall relationship between in utero exposure to tobacco smoke from maternal ETS exposure or active smoking, and development of ASD. Lay Summary: This study found that women who smoke or are exposed to tobacco smoke during pregnancy are not more likely to have children with Autism Spectrum Disorder (ASD). This is the first ASD study to measure a chemical in the mother's blood during pregnancy to identify exposure to tobacco smoke.
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In a study measuring cotinine in stored second trimester maternal serum for 499 controls and 498 ASD cases, there was no association between cotinine concentrations and odds for developing ASD among children of non-smokers (aOR: 0.93 [95% CI: 0.69, 1.25] per ng/mL).
“The results of their study found no association between cotinine concentrations and odds for developing ASD among children of non-smokers (aOR: 0.93 [95% CI: 0.69, 1.25] per ng/mL).”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [120]
In that study, there was no association between self-reported smoking (aOR: 1.64 [95% CI: 0.65, 4.16]) or cotinine-defined smoking (≥3.08 ng/mL vs <3.08 ng/mL; aOR: 0.73 [95% CI: 0.35, 1.54]) and ASD.
“Moreover, they found no associated between self-reported smoking (aOR:1.64 [95% CI: 0.65, 4.16]) or cotinine-defined smoking ( ≥ 3.08 ng/mL vs. < 3.08 ng/mL; aOR: 0.73 [95% CI: 0.35, 1.54]) and ASD [120].”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [120]
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Cites
Smoking prevalence and cigarette consumption in 187 countries, 1980-2012
Ng, M., Freeman, M. K., Fleming, T. D., Robinson, M., Dwyer-Lindgren, L., Thomson, B., Wollum, A., Sanman, E., Wulf, S., Lopez, A. D., et al. (2014) · JAMA · doi:10.1001/jama.2013.284692 · Cited by 1,576 · see citing works
Socioeconomic status and smoking: a review
Hiscock, R., Bauld, L., Amos, A., Fidler, J. A., & Munafò, M. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06202.x · Cited by 1,572 · see citing works
Huizink, A. C., & Mulder, E. J. H. (2006) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.04.005 · Cited by 468 · see citing works
Prenatal, perinatal, and postnatal factors associated with autism: A meta-analysis
Wang, C., Geng, H., Liu, W., & Zhang, G. (2017) · Medicine · doi:10.1097/md.0000000000006696 · Cited by 348 · see citing works
Prenatal factors associated with autism spectrum disorder (ASD)
Ornoy, A., Weinstein-Fudim, L., & Ergaz, Z. (2015) · Reproductive Toxicology · doi:10.1016/j.reprotox.2015.05.007 · Cited by 238 · see citing works
Prenatal, perinatal, and neonatal factors associated with autism spectrum disorders
Bilder, D., Pinborough-Zimmerman, J., Miller, J., & McMahon, W. (2009) · Pediatrics · doi:10.1542/peds.2008-0927 · Cited by 222 · see citing works
Perinatal risk factors and infantile autism
Maimburg, R. D., & Væth, M. (2006) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2006.00805.x · Cited by 192 · see citing works
Jung, Y., Lee, A. M., McKee, S. A., & Picciotto, M. R. (2017) · Scientific Reports · doi:10.1038/s41598-017-04413-1 · Cited by 77 · see citing works
Flagged first, then by citations
Research works printed but not linked: 47
- Agrawal A, Scherrer JF, Grant JD, Sartor CE, Pergadia ML, Duncan AE, Madden PAF, Haber JR, Jacob T, Bucholz KK, & Xian H (2010). The effects of maternal smoking during pregnancy on offspring outcomes. Preventive Medicine, 50(1–2), 13– 18. 20026103 PMC2813884
- Ashraf MW (2012). Levels of heavy metals in popular cigarette brands and exposure to these metals via smoking. The Scientific World Journal, 2012. https://www.hindawi.com/journals/tswj/2012/729430/. PMC3320036 22489199
- Banik A, Kandilya D, Ramya S, Stünkel W, Chong YS, & Dheen ST (2017). Maternal factors that induce epigenetic changes contribute to neurological disorders in offspring. Genes, 8 (6), 150. 28538662 PMC5485514
- Benowitz NL (1996). Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiologic Reviews, 18(2), 188– 204. 9021312
- Benowitz NL, Bernert JT, Caraballo RS, Holiday DB, & Wang J (2009). Optimal serum cotinine levels for distinguishing cigarette smokers and nonsmokers within different racial/ethnic groups in the United States between 1999 and 2004. American Journal of Epidemiology, 169(2), 236– 248. 19019851
- Bölte S, Girdler S, & Marschik PB (2019). The contribution of environmental exposure to the etiology of autism spectrum disorder. Cellular and Molecular Life Sciences, 76(7), 1275– 1297. 30570672 PMC6420889
- Burstyn I, Kapur N, Shalapay C, Bamforth F, Wild TC, Liu J, & LeGatt D (2009). Evaluation of the accuracy of self-reported smoking in pregnancy when the biomarker level in an active smoker is uncertain. Nicotine & Tobacco Research, 11(6), 670– 678. 19395685
- Burstyn I, Sithole F, & Zwaigenbaum L (2010). Autism spectrum disorders, maternal characteristics and obstetric complications among singletons born in Alberta, Canada. Chronic Diseases in Canada, 30(4), 125– 134. 20946713
- Caramaschi D, Taylor AE, Richmond RC, Havdahl KA, Golding J, Relton CL, Munafò MR, Smith GD, & Rai D (2018). Maternal smoking during pregnancy and autism: Using causal inference methods in a birth cohort study. Translational Psychiatry, 8(1), 1– 10. 30498225 PMC6265272
- Croen LA, Grether JK, Hoogstrate J, & Selvin S (2002). The changing prevalence of autism in California. Journal of Autism and Developmental Disorders, 32(3), 207– 215. 12108622
- Cunningham GC, & Tompkinson DG (1999). Cost and effectiveness of the California triple marker prenatal screening program. Genetics in Medicine, 1(5), 199– 206. 11256673
- Dietz PM, Adams MM, Kendrick JS, & Mathis MP (1998). Completeness of ascertainment of prenatal smoking using birth certificates and confidential questionnaires: Variations by maternal attributes and infant birth weight. American Journal of Epidemiology, 148(11), 1048– 1054. 9850126
- Dodds L, Fell DB, Shea S, Armson BA, Allen AC, & Bryson S (2011). The role of prenatal, obstetric and neonatal factors in the development of autism. Journal of Autism and Developmental Disorders, 41(7), 891– 902. 20922473
- Duan G, Yao M, Ma Y, & Zhang W (2014). Perinatal and background risk factors for childhood autism in central China. Psychiatry Research, 220(1–2), 410– 417. 25085792
- Dwyer JB, McQuown SC, & Leslie FM (2009). The dynamic effects of nicotine on the developing brain. Pharmacology & Therapeutics, 122(2), 125– 139. 19268688 PMC2746456
- Gould GS, Havard A, Lim LL, & Kumar R (2020). Exposure to tobacco, environmental tobacco smoke and nicotine in pregnancy: A pragmatic overview of reviews of maternal and child outcomes, effectiveness of interventions and barriers and facilitators to quitting. International Journal of Environmental Research and Public Health, 17(6), 2034. 32204415 PMC7142582
- Hultman CM, Sparén P, & Cnattingius S (2002). Perinatal risk factors for infantile autism. Epidemiology, 13(4), 417– 423. 12094096
- Jiang H, Liu L, Sun D, Yin X, Chen Z, Wu C, & Chen W (2016). Interaction between passive smoking and folic acid supplement during pregnancy on autism spectrum disorder behaviors in children aged 3 years. Zhonghua liu xing bing xue za zhi= Zhonghua liuxingbingxue zazhi, 37(7), 940– 944. 27453101
- Kalkbrenner AE, Braun JM, Durkin MS, Maenner MJ, Cunniff C, Lee L-C, Pettygrove S, Nicholas JS, & Daniels JL (2012). Maternal smoking during pregnancy and the prevalence of autism spectrum disorders, using data from the autism and developmental disabilities monitoring network. Environmental Health Perspectives, 120(7), 1042– 1048. 22534110 PMC3404663
- Kalkbrenner AE, Meier SM, Madley-Dowd P, Ladd-Acosta C, Fallin MD, Parner E, & Schendel D (2020). Familial confounding of the association between maternal smoking in pregnancy and autism spectrum disorder in offspring. Autism Research, 13(1), 134– 144. 31464107 PMC7919848
- Kim KM, Lim MH, Kwon H-J, Yoo S-J, Kim E-J, Kim JW, Ha M, & Paik KC (2018). Associations between urinary cotinine and symptoms of attention deficit/hyperactivity disorder and autism spectrum disorder. Environmental Research, 166, 481– 486. 29957501
- Kolevzon A, Gross R, & Reichenberg A (2007). Prenatal and perinatal risk factors for autism: A review and integration of findings. Archives of Pediatrics & Adolescent Medicine, 161(4), 326– 333. 17404128
- Ladd-Acosta C, Shu C, Lee BK, Gidaya N, Singer A, Schieve LA, Schendel DE, Jones N, Daniels JL, Windham GC, Newschaffer CJ, Croen LA, Feinberg AP, & Fallin MD (2016). Presence of an epigenetic signature of prenatal cigarette smoke exposure in childhood. Environmental Research, 144, 139– 148. 26610292 PMC4915563
- Lee BK, Gardner RM, Dal H, Svensson A, Galanti MR, Rai D, Dalman C, & Magnusson C (2012). Brief report: Maternal smoking during pregnancy and autism spectrum disorders. Journal of Autism and Developmental Disorders, 42(9), 2000– 2005. 22173844
- Lei G, Xi QQ, Wu J, Han Y, Dai W, Su YY, & Zhang X (2015). Association between prenatal environmental factors and child autism: A case control study in Tianjin, China. Biomedical and Environmental Sciences, 28(9), 642– 650. 26464251
- Liu D, Zhan J-Y, & Shao J (2015). Environmental risk factors for autism spectrum disorders in children. Zhongguo dang dai er ke za zhi= Chinese journal of contemporary pediatrics, 17(11), 1147– 1153. 26575869
- Lyall K, Croen L, Daniels J, Fallin MD, Ladd-Acosta C, Lee BK, Park BY, Snyder NW, Schendel D, Volk H, Windham GC, & Newschaffer C (2017). The changing epidemiology of autism spectrum disorders. Annual Review of Public Health, 38, 81– 102. PMC6566093 28068486
- Lyall K, Windham GC, Snyder NW, Kuskovsky R, Xu P, Bostwick A, Robinson L, & Newschaffer CJ (2021). Association between midpregnancy polyunsaturated fatty acid levels and offspring autism spectrum disorder in a California population-based case-control study. American Journal of Epidemiology, 190 (2), 265– 276. 33524118 PMC8086417
- Mandic-Maravic V, Coric V, Mitkovic-Voncina M, Djordjevic M, Savic-Radojevic A, Ercegovac M, Matic M, Simic T, Lecic-Tosevski D, Toskovic O, Pekmezovic T, Pljesa-Ercegovac M, & Pejovic-Milovancevic M (2019). Interaction of glutathione S-transferase polymorphisms and tobacco smoking during pregnancy in susceptibility to autism spectrum disorders. Scientific Reports, 9(1), 1– 9. 30824761 PMC6397281
- Miguel PM, Pereira LO, Silveira PP, & Meaney MJ (2019). Early environmental influences on the development of children’s brain structure and function. Developmental Medicine & Child Neurology, 61(10), 1127– 1133. 30740660
- Mrozek-Budzyn D, Majewska R, & Kieltyka A (2013). Prenatal, perinatal and neonatal risk factors for autism-study in Poland. Central European Journal of Medicine, 8(4), 424– 430.
- Nilsen RM, Surén P, Gunnes N, Alsaker ER, Bresnahan M, Hirtz D, Hornig M, Lie KK, Lipkin WI, Reichborn-Kjennerud T, Roth C, Schjølberg S, Smith GD, Susser E, Vollset SE, Øyen A-S, Magnus P, & Stoltenberg C (2013). Analysis of self-selection bias in a population-based cohort study of autism spectrum disorders. Paediatric and Perinatal Epidemiology, 27(6), 553– 563. 23919580 PMC3851582
- Pauly JR, & Slotkin TA (2008). Maternal tobacco smoking, nicotine replacement and neurobehavioural development. Acta Paediatrica, 97(10), 1331– 1337. 18554275
- Qin Y-Y, Jian B, Wu C, Jiang C-Z, Kang Y, Zhou J-X, Yang F, & Liang Y (2018). A comparison of blood metal levels in autism spectrum disorder and unaffected children in Shenzhen of China and factors involved in bioaccumulation of metals. Environmental Science and Pollution Research, 25(18), 17950– 17956. 29680891
- Saunders A, Woodland J, & Gander S (2019). A comparison of prenatal exposures in children with and without a diagnosis of autism spectrum disorder. Cureus, 11(7), e5223. 31565625 PMC6758968
- Scherer G, Conze C, Tricker A, & Adlkofer F (1992). Uptake of tobacco smoke constituents on exposure to environmental tobacco smoke (ETS). The Clinical Investigator, 70(3–4), 352– 367. 1521050
- Shea AK, & Steiner M (2008). Cigarette smoking during pregnancy. Nicotine & Tobacco Research, 10(2), 267– 278. 18236291
- Signorello LB, Cai Q, Tarone RE, McLaughlin JK, & Blot WJ (2009). Racial differences in serum cotinine levels of smokers. Disease Markers, 27(5), 187– 192. 20037205 PMC2828292
- Slotkin TA (2008). If nicotine is a developmental neurotoxicant in animal studies, dare we recommend nicotine replacement therapy in pregnant women and adolescents? Neurotoxicology and Teratology, 30(1), 1– 19. 18380035
- Toledo-Rodriguez M, Lotfipour S, Leonard G, Perron M, Richer L, Veillette S, Pausova Z, & Paus T (2010). Maternal smoking during pregnancy is associated with epigenetic modifications of the brain-derived neurotrophic factor-6 exon in adolescent offspring. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 153(7), 1350– 1354. 20583129
- Totsika V, Hastings RP, Emerson E, Lancaster GA, & Berridge DM (2011). A population-based investigation of behavioural and emotional problems and maternal mental health: Associations with autism spectrum disorder and intellectual disability. Journal of Child Psychology and Psychiatry, 52 (1), 91– 99. 20649912
- Tran PL, Lehti V, Lampi KM, Helenius H, Suominen A, Gissler M, Brown AS, & Sourander A (2013). Smoking during pregnancy and risk of autism spectrum disorder in a Finnish National Birth Cohort. Paediatric and Perinatal Epidemiology, 27 (3), 266– 274. 23574415 PMC3652271
- Vinikoor LC, Messer LC, Laraia BA, & Kaufman JS (2010). Reliability of variables on the North Carolina birth certificate: A comparison with directly queried values from a cohort study. Paediatric and Perinatal Epidemiology, 24(1), 102– 112. 20078836 PMC3437766
- Vorstman JA, Parr JR, Moreno-De-Luca D, Anney RJ, Nurnberger JI Jr., & Hallmayer JF (2017). Autism genetics: Opportunities and challenges for clinical translation. Nature Reviews Genetics, 18(6), 362. 28260791
- Windham GC, Anderson MC, Croen LA, Smith KS, Collins J, & Grether JK (2011). Birth prevalence of autism spectrum disorders in the San Francisco Bay area by demographic and ascertainment source characteristics. Journal of Autism and Developmental Disorders, 41(10), 1362– 1372. 21264681
- Zablotsky B, Black LI, & Blumberg SJ (2017). Estimated prevalence of children with diagnosed developmental disabilities in the United States, 2014–2016. NCHS Data Brief, no 291. Hyattsville, MD: National Center for Health Statistics. https://www.cdc.gov/nchs/products/databriefs/db291.htm?fbclid=IwAR0MwhWDgawPU 29235982
- Zhang X, Lv C-C, Tian J, Miao R-J, Xi W, Hertz-Picciotto I, & Qi L (2010). Prenatal and perinatal risk factors for autism in China. Journal of Autism and Developmental Disorders, 40(11), 1311– 1321. 20358271 PMC2974190
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Wells, A. C., & Lotfipour, S. (2023) · Advances in Drug and Alcohol Research · doi:10.3389/adar.2023.11628 · Cited by 50 · see citing works
- Authors
- Berger, K., Pearl, M., Kharrazi, M., Li, Y., DeGuzman, J., She, J., Behniwal, P., Lyall, K., & Windham, G.
- Affiliations
- Sequoia Foundation (US)
- California Department of Public Health (US)
- Environmental Health Investigations Branch California Department of Public Health Richmond California USA
- Drexel University (US)
- Corresponding author
- Berger, Kimberly
- Venue
- Autism Research
- Publisher
- Wiley
- Published
- 2021-06-24
- Volume
- 14
- Issue
- 9
- Pages
- 2017-2026
- ISSN
- 1939-3792 (ISSN-L)
- 1939-3806
- PMC
- PMC10752221
- OpenAlex
- W3176310078
- Cited by
- 15
- References
- 8
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 1
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Autism Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (K22 ES026235, R03 CA211820)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- autism spectrum disorder, environmental tobacco smoke, smoking during pregnancy, serum cotinine, maternal serum, second trimester
- MeSH terms
- Autism Spectrum Disorder, Child, Cotinine, Female, Humans, Pregnancy, Smoking, Tobacco Smoke Pollution, Maternal Exposure
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