Does Maternal Prescription Opioid Use during Pregnancy Increase a Child’s Risk of ASD or Developmental Disability?

Background: Opioid use among pregnant women has increased along with the stark rise in US opioid prescribing rates from 1999 to 2015. While opioid use during pregnancy has been associated with poor pregnancy outcomes, including neonatal abstinence syndrome, preterm birth and some congenital malformations, little is known about maternal opioid use during pregnancy and the child’s risk of neurodevelopmental conditions, such as autism spectrum disorder (ASD) or non-ASD developmental disability (DD).

Objectives: Examine associations between maternal prescription opioid use during pregnancy (from three months preconception to delivery), and ASD, DD without ASD features, or autism traits (either ASD or DD with ASD features) in children enrolled in the Study to Explore Early Development (SEED).

Methods:

: SEED is a multi-site case-control study of ASD risk factors and phenotype in children aged 3-5 years, from 2003 to 2011. Children with ASD or other DDs were identified from schools and healthcare providers. Population controls (POP) were randomly sampled from birth certificates at each site. ASD case status was confirmed with a developmental evaluation that included the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Children receiving the ASD evaluation but not meeting SEED criteria for ASD were identified as having DD with ASD features. Children with DD diagnoses who did not have a SEED ASD evaluation were considered to have DD without ASD features. To evaluate autism traits independent of meeting a diagnostic threshold for ASD, we combined the ASD and the DD with ASD features groups. Maternal prescription opioid use and timing of use were determined by prescriptions abstracted from maternal prenatal care medical records. Study children included 1369 with ASD, 1414 with other DDs (938 without ASD features), and 1577 POP. We calculated odds ratios (ORs) using logistic regression adjusted for confounders affecting estimated ORs by >10% (maternal race/ethnicity, maternal education, smoking, depression, and study year) comparing cases (ASD, DD without ASD features, autism traits) to POP by prescription opioid exposure (any use, use in three months preconception, by trimester).

Results:

Overall, mothers of 7.7% (N=336) of study children were given prescription opioids just before or during pregnancy. In unadjusted analyses, prescription opioid use, preconception or during pregnancy, was associated with ASD (OR 1.56, 95% confidence interval [CI]: 1.19, 2.06) and autism features (OR: 1.61, CI: 1.24, 2.08), driven largely by exposure prior to and during the first trimester. After adjustment, ORs for use during any period were attenuated for the ASD (OR: 1.27, CI: 0.95, 1.69) and autism features (OR: 1.31, CI: 1.00, 1.72) groups. In all groups, adjusted ORs for prescription opioid use preconception were greater than 1.95 but only statistically significant for the autism features group (OR: 2.58, CI: 1.08, 6.16).

Conclusions: Maternal prescription opioid use just before or early in pregnancy led to increased odds of ASD, a statistically significant association with autism features, and no association with DD without ASD features. Findings may suggest etiologic pathways involving placental or fetal exposure that lead to ASD and DD, but may also be attributable to unmeasured or residual confounding.