Trajectories of prenatal alcohol exposure and behavioral outcomes: Findings from a community-based sample.

OBJECTIVE: To characterize patterns of prenatal alcohol exposure (PAE), and determine whether PAE trajectories were associated with behavior from a community-based sample of first-grade children. METHODS: Using data collected as part of the Collaboration of Fetal Alcohol Spectrum Disorders Prevalence study (n = 1663), we performed longitudinal cluster analysis on prenatal alcohol use reported for four time points around conception and pregnancy. From the sample, 638 respondents reported any alcohol use in pregnancy and were included in trajectories for average daily and maximum drinks per drinking day (max DDD). We then estimated the association with behavioral problems measured by the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF) with multivariable linear regression. The reference group had 1025 children with no reported PAE. RESULTS: Five trajectories were selected to describe max DDD patterns: very low/discontinuing (n = 186), low/discontinuing (n = 111), very low/continuing (n = 47), med/high (n = 245), and high (n = 49). Six trajectories best described average daily alcohol use: very low/discontinuing (n = 378), very low/continuing (n = 98), low/continuing (n = 56), low/discontinuing (n = 37), medium/high (n = 35), and high (n = 31). When assessing max DDD trajectories for both the CBCL and TRF, individuals with PAE in the two highest trajectories and the very low/continuing trajectory had more behavioral problems relative to children with no PAE, although confidence intervals for most estimates included the null. PAE modeled as average drinks per day did not predict behavior in any consistent pattern. CONCLUSIONS: In this community-based sample, select PAE trajectories were associated with behavior, even at relatively low levels of PAE that continued later in gestation.

The enduring impact of neurulation stage alcohol exposure: A combined behavioral and structural neuroimaging study in adult male and female C57BL/6J mice.

Prenatal alcohol exposure (PAE) can cause behavioral and brain alterations over the lifespan. In animal models, these effects can occur following PAE confined to critical developmental periods, equivalent to the third and fourth weeks of human gestation, before pregnancy is usually recognized. The current study focuses on PAE during early neurulation and examines the behavioral and brain structural consequences that appear in adulthood. On gestational day 8 C57BL/6J dams received two alcohol (2.8g/kg, i.p), or vehicle, administrations, four hours apart. Male and female offspring were reared to adulthood and examined for performance on the elevated plus maze, rotarod, open field, Morris water maze, acoustic startle, social preference (i.e. three-chambered social approach test), and the hot plate. A subset of these mice was later evaluated using magnetic resonance imaging to detect changes in regional brain volumes and shapes. In males, PAE increased exploratory behaviors on the elevated plus maze and in the open field; these changes were associated with increased fractional anisotropy in the anterior commissure. In females, PAE reduced social preference and the startle response, and decreased cerebral cortex and brain stem volumes. Vehicle-treated females had larger pituitaries than did vehicle-treated males, but PAE attenuated this sex difference. In males, pituitary size correlated with open field activity, while in females, pituitary size correlated with social activity. These findings indicate that early neurulation PAE causes sex specific behavioral and brain changes in adulthood. Changes in the pituitary suggest that this structure is especially vulnerable to neurulation stage PAE.