Association Between Antenatal Antimicrobial Therapy and Autism Spectrum Disorder-A Nested Case-Control Study

Nitzan Abelson; Gal Meiri; Shirley Solomon; Hagit Flusser; Analya Michaelovski; Ilan Dinstein; Idan Menashe

doi:10.3389/fpsyt.2021.771232

Association Between Antenatal Antimicrobial Therapy and Autism Spectrum Disorder-A Nested Case-Control Study

Front Psychiatry. 2021 Nov 19:12:771232. doi: 10.3389/fpsyt.2021.771232. eCollection 2021.

Authors

Nitzan Abelson¹, Gal Meiri^{2

3}, Shirley Solomon³, Hagit Flusser^{3

4}, Analya Michaelovski^{3

4}, Ilan Dinstein^{3

5

6}, Idan Menashe^{3

6

7}

Affiliations

¹ Joyce & Irving Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, and Soroka University Medical Center, Beer-Sheva, Israel.
² Pre-School Psychiatry Unit, Soroka University Medical Center, Beer-Sheva, Israel.
³ National Autism Research Center of Israel, Beer-Sheva, Israel.
⁴ Child Development Center, Soroka University Medical Center, Beer-Sheva, Israel.
⁵ Psychology Department, and Cognitive and Brain Sciences Department, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
⁶ Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
⁷ Public Health Department, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Abstract

Background: Multiple prenatal factors have been associated with autism spectrum disorder (ASD) risk. However, current data about the association between antimicrobial use during pregnancy and ASD is limited. Methods: A nested matched case-control study of children with ASD (cases), and children without ASD or other psychiatric or genetic disorders (controls). We compared the use of antimicrobial therapy during the 3 months before conception or during pregnancy between mothers of cases and controls and used multivariate conditional logistic regression models to assess the independent association between maternal use of antimicrobials during pregnancy and the risk of ASD in their offspring. Results: More than half of the mothers in the study (54.1%) used antimicrobial drugs during the 3 months before conception or during pregnancy. Rates of antimicrobial use were lower for mothers of children with ASD compared to mothers of controls (49.0 vs. 55.1%, respectively; p = 0.02), especially during the third trimester of pregnancy (18.8 vs. 22.9%, respectively; p = 0.03), and for the use of penicillins (15.7 vs. 19.7%, respectively; p = 0.06). These case-control differences suggest that antimicrobial administration during pregnancy was associated with a reduced risk of ASD in the offspring (aOR = 0.75, 95% CI = 0.61-0.92). Interestingly, this association was seen only among Jewish but not for the Bedouin mothers (aOR = 0.62, 95% CI = 0.48-0.79 and aOR = 1.21, 95% CI = 0.82-1.79). Conclusions: The reduced risk of ASD associated with prenatal antimicrobials use only in the Jewish population suggest the involvement of other ethnic differences in healthcare services utilization in this association.

Keywords: Autism spectrum disorder (ASD); antimicrobial drugs; ethnic disparities; prenatal; public health.