Objectives: We estimated average ASD population attributable fractions (PAFs) for three perinatal risk factors (preterm delivery, small-for-gestational-age [SGA], and Cesarean delivery [CD]) and the summary PAFs for all factors considered together among US-children born in 1994 and 2000. Average PAF estimates account for co-occurrence of multiple risk factors in addition to adjusting for other potential confounding factors; thus, average PAFs address the inherent bias introduced when separate adjusted PAFs are computed for each factor of interest.
We chose three perinatal factors that could feasibly make a substantive contribution to the population ASD burden because they are both associated with ASD and prevalent in the population. However, each factor represents a composite of multiple potential underlying etiologic mechanisms. Their PAF estimates are thus best interpreted as the proportion of ASD that may be attributable to having a sub-optimal perinatal environment that results in preterm, SGA, and/or CD.
Methods: Cases were singleton non-Hispanic white, non-Hispanic black, and Hispanic children born in 1994 (n=703) or 2000 (n=1339) who resided at birth and age 8 years in 48 US counties within 8 ADDM sites. They were identified as having ASDs using a common methodology based on health/education record review. Each case was matched to 20 controls from the US natality files on birth year, sex, and mother’s county of residence, race-ethnicity, age, and education. Adjusted odds ratios (aORs) for associations between ASD and each perinatal factor and ASD and a summary variable of one or more factors were estimated using conditional logistic regression. Component aORs were analogously estimated for all possible separate and joint effects of the three factors. These aOR estimates, and the appropriate proportions of exposed cases, were used to derive sequential and subsequently average PAFs. 95% confidence limits (CLs) for PAFs were estimated using a bootstrap technique.
Results: Overall, aORs for each perinatal factor were 1.3-1.4 for both birth cohorts with the exception of SGA for the 1994 cohort (aOR=1.1). For the 1994 birth cohort, average PAFs for preterm, SGA, and CD were 4.2%, 0.9%, and 7.9% respectively, with a summary PAF of 13.0% (1.7%-19.5%) for any of the three factors. For the 2000 birth cohort, average PAFs for preterm, SGA, and CD were 2.0%, 3.1%, and 6.7% respectively, with a summary PAF of 11.8% (7.5%-15.9%). Subgroup analyses among both birth cohorts were suggestive of a slightly higher summary PAF among children with both ASD and co-occurring intellectual disability (ID); however, CLs for subgroups with and without ID overlapped.
Conclusions: 12-13% of ASDs among children born in 1994 or 2000 in the 48 US counties represented in this analysis were attributable to preterm, SGA, and/or CD (and their underlying pathways). Despite some fluctuations in PAFs for individual factors, there was no change over time in the summary PAF for these three factors.
See more of: Epidemiology
See more of: Prevalence, Risk factors & Intervention