Maternal Prenatal Smoking and Autism Spectrum Disorder in Offspring

A California Statewide Cohort and Sibling Study

Ondine S. von Ehrenstein; Xin Cui; Qi Yan; Hilary Aralis; Beate Ritz


Am J Epidemiol. 2021;190(5):728-737. 

In This Article


Characteristics of the full cohort, and of the case-sibling subcohort, are displayed by case status in Table 1 and by smoking status in Web Table 1 (available at Case mothers were on average older than noncase mothers, more educated, and less frequently identified as Latina/Hispanic compared with mothers of noncases in the full cohort (Table 1). These demographic factors were similar for cases with and without a sibling born during the study period (Web Table 2). Among cases with a sibling, demographic characteristics were similar comparing autism cases with and without intellectual disability comorbidity (Web Table 3). Demographic characteristics of the "all siblings" noncases and the full cohort or the case-sibling controls were also similar (Web Table 4).

In the full cohort, we estimated an adjusted odds ratio for ASD in relation to smoking 3 months before or during pregnancy ("ever smokers") of 1.15 (95% CI: 1.04, 1.26) compared with nonsmoking mothers. Odds ratios for smoking only prior to pregnancy, and prior and during pregnancy ("continuous smokers"), were similarly elevated (Table 2). The point estimates for maternal smoking and ASD in the sibling comparison were generally similar but less stable, and the 95% confidence intervals were wide due to the relatively small number of discordant sibling pairs (Table 2).

For heavier smokers (≥20 cigarettes/day), we estimated elevated odds ratios in the full cohort and in the sibling comparison. Smoking 20 or more cigarettes/day during any trimester period during pregnancy was associated with greater odds (odds ratio = 1.55, 95% CI: 1.21, 1.98) for developing the disorder in the full cohort. The estimated association related to 1–19 cigarettes/day was weaker (Table 2).

Stratifying by intellectual disability comorbidity for ever-smoking, estimated odds ratios were similar for cases with intellectual disability (odds ratio = 1.12, 95% CI: 0.84, 1.49) and without (odds ratio = 1.15, 95% CI: 1.04, 1.27) in the full cohort (Table 3). In the sibling comparisons, numbers in some cells were too small for models to converge (among "with intellectual disability") and generally 95% confidence intervals were wide (Table 3).

In sensitivity analyses, restricting to term births or to cases diagnosed by age 3 years, or not adjusting for pregnancy complications, did not change our estimated associations appreciably (data not shown). We also evaluated the entire sample of siblings within the full cohort. Compared with case-family siblings, estimated odds ratios based on all siblings (by design not a "sibling comparison") were generally similar; all confidence intervals were wide and overlapped (Web Table 5).