TY - JOUR
T1 - Familial confounding of the association between maternal smoking in pregnancy and autism spectrum disorder in offspring
AU - Kalkbrenner, Amy E.
AU - Meier, Sandra M.
AU - Madley-Dowd, Paul
AU - Ladd-Acosta, Christine
AU - Fallin, Margaret Daniele
AU - Parner, Erik
AU - Schendel, Diana
N1 - Funding Information:
Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award No. R01ES026993. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support came from an unrestricted grant from the Lundbeck Foundation (iPSYCH).
Publisher Copyright:
© 2019 International Society for Autism Research, Wiley Periodicals, Inc.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Evidence supports no link between maternal smoking in pregnancy and autism spectrum disorder (autism) overall. To address remaining questions about the unexplained heterogeneity between study results and the possibility of risk for specific autism sub-phenotypes, we conducted a whole-population cohort study in Denmark. We followed births 1991–2011 (1,294,906 persons, including 993,301 siblings in 728,271 families), from 1 year of age until an autism diagnosis (13,547), death, emigration, or December 31, 2012. Autism, with and without attention deficit hyperactivity disorder (ADHD) and with and without intellectual disability (ID) were based on ICD-8 and ICD-10 codes from Danish national health registers, including 3,319 autism + ADHD, 10,228 autism − no ADHD, 2,205 autism + ID, and 11,342 autism − no ID. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) between any maternal smoking (from birth records) and autism (or sub-phenotypes) using survival models with robust standard errors, stratifying by birth year and adjusting for child sex, parity, and parental age, education, income, and psychiatric history. To additionally address confounding using family designs, we constructed a maternal cluster model (adjusting for the smoking proportion within the family), and a stratified sibling model. Associations with maternal smoking and autism were elevated in conventional adjusted analyses (HR of 1.17 [1.13–1.22]) but attenuated in the maternal cluster (0.98 [0.88–1.09]) and sibling (0.86 [0.64–1.15]) models. Similarly, risks of autism sub-phenotypes with maternal smoking were attenuated in the family-based models. Together these results support that smoking in pregnancy is not linked with autism or select autism comorbid sub-phenotypes after accounting for familial confounding. Autism Res 2020, 13: 134–144.
AB - Evidence supports no link between maternal smoking in pregnancy and autism spectrum disorder (autism) overall. To address remaining questions about the unexplained heterogeneity between study results and the possibility of risk for specific autism sub-phenotypes, we conducted a whole-population cohort study in Denmark. We followed births 1991–2011 (1,294,906 persons, including 993,301 siblings in 728,271 families), from 1 year of age until an autism diagnosis (13,547), death, emigration, or December 31, 2012. Autism, with and without attention deficit hyperactivity disorder (ADHD) and with and without intellectual disability (ID) were based on ICD-8 and ICD-10 codes from Danish national health registers, including 3,319 autism + ADHD, 10,228 autism − no ADHD, 2,205 autism + ID, and 11,342 autism − no ID. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) between any maternal smoking (from birth records) and autism (or sub-phenotypes) using survival models with robust standard errors, stratifying by birth year and adjusting for child sex, parity, and parental age, education, income, and psychiatric history. To additionally address confounding using family designs, we constructed a maternal cluster model (adjusting for the smoking proportion within the family), and a stratified sibling model. Associations with maternal smoking and autism were elevated in conventional adjusted analyses (HR of 1.17 [1.13–1.22]) but attenuated in the maternal cluster (0.98 [0.88–1.09]) and sibling (0.86 [0.64–1.15]) models. Similarly, risks of autism sub-phenotypes with maternal smoking were attenuated in the family-based models. Together these results support that smoking in pregnancy is not linked with autism or select autism comorbid sub-phenotypes after accounting for familial confounding. Autism Res 2020, 13: 134–144.
KW - attention deficit hyperactivity disorder
KW - autism
KW - autism spectrum disorder
KW - confounding
KW - family-based designs
KW - intellectual disability
KW - maternal smoking
KW - neurodevelopment
KW - tobacco
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U2 - 10.1002/aur.2196
DO - 10.1002/aur.2196
M3 - Article
C2 - 31464107
AN - SCOPUS:85071572976
SN - 1939-3792
VL - 13
SP - 134
EP - 144
JO - Autism Research
JF - Autism Research
IS - 1
ER -