Date of Award

Spring 2021

Document Type

Open Access Dissertation

Department

Epidemiology and Biostatistics

First Advisor

Suzanne McDermott

Second Advisor

Anwar Merchant

Abstract

Neurodevelopmental disorders in children including Autism Spectrum Disorders (ASD) and Intellectual disability (ID) are the topics of growing concern and recently many studies looked for the risk factors of these disorders. Although antidepressants and antiepileptics consumption during pregnancy have been reported to be associated with ASD, the effect of NSAID or acetaminophen, two most common drugs used during pregnancy, have been under researched. We conducted a prospective cohort study linking data from Medicaid, Department of Education, and Department of Disabilities and Special Needs with birth certificate data from mothers and children between 2010-2017. Beside exposure variables, NSAID and acetaminophen, and outcome variables, ASD and ID, other covariates included were maternal age, race, BMI, preeclampsia, gestational diabetes, smoking, and infection which were ascertained using causal diagram. Later. we measured the direct and indirect effects of NSAID use on ID. For acetaminophen, we conducted systematic review and meta-analysis because of the underrepresentation of acetaminophen prescription in our data sources. There were 153,562 mother-child pairs of whom 3859 mothers were exposed to NSAID prescription during pregnancy, and the rest were unexposed. Regarding the outcome variable, 1018 children were flagged as ASD only, 6300 as ID only, and 1939 children had ASD with ID. Our main exposure variable, NSAID prescription was associated with ID with an adjusted odds ratio of 1.52. The sensitivity analysis also gave us similar findings. We found a significant mediation effect of birthweight on ID. Very low birth weight mediated the association of NSAIDs on ID (OR:1.21, 95% CI: 1.06 – 1.40) when 40.9% of the effects of NSAIDs on ID was mediated through very low birthweight. When we categorized birthweight as low birth weight versus others, the direct effect was 1.42 (95% CI: 1.03-1.96) and the indirect effect was 1.10 (95% CI: 1.06-1.15) and 27.1% of the effects were mediated. The systematic review included 67,319 mother-child dyads in total. There was heterogeneity among the studies (I2: 94%). The pooled odds ratio for the association between acetaminophen exposure during pregnancy and ASD in the child was 1.29 (95% CI: 1.17, 1.41). Our findings warrant further research on the research question and inform the scientific community and the relevant stakeholders regarding the risks of taking NSAIDs and acetaminophen.

Available for download on Monday, May 15, 2023

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