Association of adverse prenatal exposure burden with child psychopathology in the Adolescent Brain Cognitive Development (ABCD) Study

Abstract

Objective Numerous adverse prenatal exposures have been individually associated with risk for psychiatric illness in the offspring. However, such exposures frequently co-occur, raising questions about their cumulative impact. We evaluated effects of cumulative adverse prenatal exposure burden on psychopathology risk in school-aged children. Methods Using baseline surveys from the U.S.-based Adolescent Brain and Cognitive Development (ABCD) Study (7,898 non-adopted, unrelated children from 21 sites, age 9–10, and their primary caregivers), we examined 8 retrospectively-reported adverse prenatal exposures in relation to caregiver-reported total and subscale Child Behavior Checklist (CBCL) scores. We also assessed cumulative effects of these factors on CBCL total as a continuous measure, as well as on odds of clinically significant psychopathology (CBCL total ≥60), in both the initial set and a separate ABCD sample comprising an additional 696 sibling pairs. Analyses were conducted before and after adjustment for 14 demographic and environmental covariates. Results In minimally and fully adjusted models, 6 exposures (unplanned pregnancy; maternal alcohol, marijuana, and tobacco use early in pregnancy; pregnancy complications; and birth complications) independently associated with significant but small increases in CBCL total score. Among these 6, none increased the odds of crossing the threshold for clinically significant symptoms by itself. However, odds of exceeding this threshold became significant with 2 exposures (OR = 1.86, 95% CI 1.47–2.36), and increased linearly with each level of exposure (OR = 1.39, 95% CI 1.31–1.47), up to 3.53-fold for ≥4 exposures versus none. Similar effects were observed in confirmatory analysis among siblings. Within sibling pairs, greater discordance for exposure load associated with greater CBCL total differences, suggesting that results were not confounded by unmeasured family-level effects. Conclusion Children exposed to multiple common, adverse prenatal events showed dose-dependent increases in broad, clinically significant psychopathology at age 9–10. Fully prospective studies are needed to confirm and elaborate upon this pattern.

Cumulative environmental risk in early life is associated with mental disorders in childhood

“…In conclusion, we show here that cumulative exposure to risk in early childhood, as determined from routinely collected administrative data, is associated with the full range of mental disorders in middle childhood. This extends previous research showing that prenatal factors (Roffman et al, 2021), neighbourhood factors (Theall et al, 2012), and experiences of trauma or neglect (Hughes et al, 2017) are associated with mental disorders by demonstrating their cumulative effects on risk for mental disorders. Further, the relationship between cumulative environmental risk and mental disorder appears to be a transdiagnostic risk factor associated with all categories of childhood mental disorders.…”

“…However, proximal exposures of trauma and neglect are not the only environmental exposures to act cumulatively. There is also evidence that prenatal exposures act cumulatively to predict childhood psychopathology (Roffman et al, 2021), as do neighbourhood risk factors (Theall, Drury, & Shirtcliff, 2012). It is therefore important to understand the cumulative impacts of a range of both proximal (direct) and distal (indirect) risk factors that commonly co-occur, and which may be causally linked or reflect shared background factors (e.g.…”

Neuropsychopharmacology reviews 2022 hot topics: the prenatal environment and risk for mental illness in young people

“…Although adverse prenatal exposures can have large effects (~1.5–2-fold increased risk of disease), these exposures are also common and frequently co-occur, raising questions about additive effects. Using Adolescent Brain Cognitive Development (ABCD) Study data, we assessed cumulative effects of adverse prenatal exposures on psychopathology at ages 9–10 [ 1 ]. Each adversity associated independently with modest effects on psychopathology scores.…”

The Exposome and its Associations with Broad Mental and Physical Health Measures in Early Adolescence

“…A key example of this phenomenon in the analysis is the prenatal exposure items, from which items split between the household adversity subfactor (prenatal exposure to substances, planned pregnancy) and the pregnancy/birth complications subfactor. Notably, growing efforts try to link pre-/post-natal exposures in the ABCD Study with developmental outcomes (prenatal cannabis exposure 23 , breastfeeding 56 and other prenatal adversities 57 ). Hence it will become increasingly important to rigorously account for exposome complexity to allow generalizability and replicability of findings and identify causal mechanisms that are not confounded by collinear exposures.…”