Abstract
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. 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. 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. 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.
Highlights
Long held neurodevelopmental theories posit that risk for serious mental illness begins early in life
Children exposed to multiple common, adverse prenatal events showed dose-dependent increases in broad, clinically significant psychopathology at age 9–10
Across both retrospective and prospective studies, adverse prenatal exposures that occur more frequently, such as pregnancy or birth complications [8, 9], prematurity [10], maternal infections [11, 12], and maternal substance or tobacco use [13,14,15,16,17,18,19,20] have associated with a range of psychopathology, including disorders that emerge during childhood
Summary
Long held neurodevelopmental theories posit that risk for serious mental illness begins early in life. Some well-known birth cohort studies have shown that offspring exposed to starvation in utero during the Dutch Hunger Winter [6] and the Chinese famine of 1959–61 [7] had a 2-fold increased risk of psychotic illness two decades later Across both retrospective and prospective studies, adverse prenatal exposures that occur more frequently, such as pregnancy or birth complications [8, 9], prematurity [10], maternal infections (including both serious infections such as influenza, and more minor ones such as urinary tract infections) [11, 12], and maternal substance or tobacco use [13,14,15,16,17,18,19,20] have associated with a range of psychopathology, including disorders that emerge during childhood. Heavy alcohol use throughout pregnancy has been found to associate with greater psychopathology than occasional use [22]
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