TY - JOUR
T1 - Interaction between Maternal Immune Activation and Antibiotic Use during Pregnancy and Child Risk of Autism Spectrum Disorder
AU - Holingue, Calliope
AU - Brucato, Martha
AU - Ladd-Acosta, Christine
AU - Hong, Xiumei
AU - Volk, Heather
AU - Mueller, Noel T.
AU - Wang, Xiaobin
AU - Fallin, M. Daniele
N1 - Funding Information:
This study is supported in part by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant number R40MC27443, Autism Field‐initiated Innovative Research Studies Program; and grant number UJ2MC31074, Autism Single Investigator Innovation Program. The Boston Birth Cohort (the parent study) was supported in part by the National Institutes of Health (NIH) grants (R21ES011666, R21HD066471, U01AI090727, R21AI079872, R01HD086013, 2R01HD041702, and R01HD098232). CBH was supported by the National Institute of Mental Health Psychiatric Epidemiology Training Program (5T32MH014592; PI Peter Zandi). NTM was supported by National Heart, Lung, and Blood Institute of the NIH grant K01HL141589. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or the U.S. Government. The funding agencies had no involvement in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Funding Information:
This study is supported in part by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant number R40MC27443, Autism Field-initiated Innovative Research Studies Program; and grant number UJ2MC31074, Autism Single Investigator Innovation Program. The Boston Birth Cohort (the parent study) was supported in part by the National Institutes of Health (NIH) grants (R21ES011666, R21HD066471, U01AI090727, R21AI079872, R01HD086013, 2R01HD041702, and R01HD098232). CBH was supported by the National Institute of Mental Health Psychiatric Epidemiology Training Program (5T32MH014592; PI Peter Zandi). NTM was supported by National Heart, Lung, and Blood Institute of the NIH grant K01HL141589. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or the U.S. Government. The funding agencies had no involvement in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Publisher Copyright:
© 2020 International Society for Autism Research and Wiley Periodicals LLC.
PY - 2020/12
Y1 - 2020/12
N2 - Prenatal exposure to maternal immune activation (MIA) has been implicated as a risk factor for the development of autism spectrum disorder (ASD), though the conditions under which this elevated risk occurs are unclear. Animal literature demonstrates that antibiotic use, which affects the composition of the maternal gut microbiota, modifies the effect of MIA on neurodevelopmental outcomes in the offspring. The aim of this study was to assess whether antibiotic use during pregnancy modifies the association between MIA and subsequent risk of ASD, in a prospective birth cohort with 116 ASD cases and 860 typically developing (TD) child controls. There was no evidence of interaction between fever or genitourinary infection and antibiotic use on the odds of ASD in unadjusted or adjusted analyzes. However, we found evidence of an interaction between flu, specifically in second trimester, and antibiotic use at any point during pregnancy on the odds of ASD in the child. Among women who received an antibiotic during pregnancy, flu in trimester two was not associated with ASD (adjusted odds ratio [aOR] = 0.99 [0.43–2.28]). Among women who were not exposed to an antibiotic at any point during pregnancy, flu in second trimester was significantly associated with increased odds of ASD (aOR = 4.05 [1.14–14.38], P =.03), after adjustment for child sex, child birth year, maternal age, gestational age, C-section delivery, and low birthweight. These findings should be treated as hypothesis-generating and suggest that antibiotic use may modify the influence that MIA has on autism risk in the child. Lay Summary: We looked at whether the association between activation of the immune system during pregnancy and risk of the child developing autism spectrum disorder (ASD) differed among women who did or did not take an antibiotic at any point during pregnancy. We examined 116 children with ASD and 860 without ASD and found that flu in second trimester was associated with increased ASD, but only among women who did not take an antibiotic during pregnancy. No other immune activation exposures seemed to interact with antibiotic use.
AB - Prenatal exposure to maternal immune activation (MIA) has been implicated as a risk factor for the development of autism spectrum disorder (ASD), though the conditions under which this elevated risk occurs are unclear. Animal literature demonstrates that antibiotic use, which affects the composition of the maternal gut microbiota, modifies the effect of MIA on neurodevelopmental outcomes in the offspring. The aim of this study was to assess whether antibiotic use during pregnancy modifies the association between MIA and subsequent risk of ASD, in a prospective birth cohort with 116 ASD cases and 860 typically developing (TD) child controls. There was no evidence of interaction between fever or genitourinary infection and antibiotic use on the odds of ASD in unadjusted or adjusted analyzes. However, we found evidence of an interaction between flu, specifically in second trimester, and antibiotic use at any point during pregnancy on the odds of ASD in the child. Among women who received an antibiotic during pregnancy, flu in trimester two was not associated with ASD (adjusted odds ratio [aOR] = 0.99 [0.43–2.28]). Among women who were not exposed to an antibiotic at any point during pregnancy, flu in second trimester was significantly associated with increased odds of ASD (aOR = 4.05 [1.14–14.38], P =.03), after adjustment for child sex, child birth year, maternal age, gestational age, C-section delivery, and low birthweight. These findings should be treated as hypothesis-generating and suggest that antibiotic use may modify the influence that MIA has on autism risk in the child. Lay Summary: We looked at whether the association between activation of the immune system during pregnancy and risk of the child developing autism spectrum disorder (ASD) differed among women who did or did not take an antibiotic at any point during pregnancy. We examined 116 children with ASD and 860 without ASD and found that flu in second trimester was associated with increased ASD, but only among women who did not take an antibiotic during pregnancy. No other immune activation exposures seemed to interact with antibiotic use.
KW - anti-bacterial agents
KW - autism spectrum disorder
KW - environmental exposure
KW - epidemiology
KW - maternal exposure
KW - minority health
KW - risk factors
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U2 - 10.1002/aur.2411
DO - 10.1002/aur.2411
M3 - Article
C2 - 33067915
AN - SCOPUS:85092581229
SN - 1939-3806
VL - 13
SP - 2230
EP - 2241
JO - Autism Research
JF - Autism Research
IS - 12
ER -