Evaluation of Brain Alterations and Behavior in Children With Low Levels of Prenatal Alcohol Exposure

Long X, Lebel C. Evaluation of Brain Alterations and Behavior in Children With Low Levels of Prenatal Alcohol Exposure. JAMA Netw Open. 2022;5(4):e225972. doi:10.1001/jamanetworkopen.2022.5972

Key Points

Question  How do brain structure and behavior of children with low levels of prenatal alcohol exposure (PAE) differ compared with those of a well-matched control group of children?

Findings  In this cross-sectional study of 135 children with low levels of PAE and 135 unexposed controls, children with PAE had worse externalizing behavior scores and lower fractional anisotropy in several white matter areas of the brain compared with children in the control group. Higher fractional anisotropy was associated with less problematic behavior in the control group, but no association was found in the PAE group.

Meaning  These findings suggest that even small amounts of PAE are associated with structural brain alterations, highlighting the importance of evidence-based policy making and underscoring the need to consider prenatal exposures in future studies of pediatric brain development.


Importance  High levels of prenatal alcohol exposure (PAE) are associated with widespread behavioral and cognitive problems as well as structural alterations of the brain. However, it remains unclear whether low levels of PAE affect brain structure and function, and prior studies generally have not had well-matched control populations (eg, for sociodemographic variables).

Objective  To compare structural brain alterations and behavioral changes in children with lower levels of PAE with those of well-matched controls with no PAE.

Design, Setting, and Participants  In this cross-sectional study, participants were selected from the Adolescent Brain Cognitive Development study. Children with PAE were compared with controls matched for age, sex, family income, maternal educational level, and caregiver status. Neither group had prenatal exposure to other adverse substances (eg, tobacco, cannabis, illicit drugs). Data were collected from September 1, 2016, to November 15, 2018, and analyzed from October 14, 2020, to February 14, 2022.

Exposures  Diffusion tensor imaging, resting-state functional magnetic resonance imaging (MRI), and Child Behavior Checklist (CBCL) administration.

Main Outcomes and Measures  Fractional anisotropy (FA); mean, axial, and radial diffusivity from diffusion tensor imaging; brain functional signal variations from functional MRI; and several scores, including internalizing and externalizing behavior problems, from the CBCL. Spearman correlation coefficients between diffusion tensor imaging and functional MRI measures and the CBCL scores were calculated.

Results  A total of 270 children were included in the analysis (mean [SD] age, 9.86 [0.46] years; 141 female [52.2%] and 129 male [47.8%]), consisting of 135 children with PAE (mean [SD] age, 9.85 [0.65] years; 73 female [54.1%] and 62 male [45.9%]) (mean exposure, 1 drink/wk) and 135 unexposed controls (mean [SD] age, 9.87 [0.04] years; 68 female [50.4%] and 67 male [49.6%]). Children with PAE had lower mean (SD) FA in white matter of the left postcentral (0.35 [0.05] vs 0.36 [0.04]; mean difference, −0.02 [95% CI, −0.03 to −0.01]), left inferior parietal (0.31 [0.07] vs 0.33 [0.06]; mean difference, −0.03 [95% CI, −0.04 to −0.01]), left planum temporale (0.26 [0.04] vs 0.28 [0.03]; mean difference, −0.02 [95% CI, −0.03 to −0.01]), left inferior occipital (0.30 [0.07] vs 0.32 [0.05]; mean difference, −0.03 [95% CI, −0.04 to −0.01]), and right middle occipital (0.30 [0.04] vs 0.31 [0.04]; mean difference, −0.01 [95% CI, −0.02 to −0.01]) areas compared with controls, and higher FA in the gray matter of the putamen (0.22 [0.03] vs 0.21 [0.02]; mean difference, 0.01 [95% CI, 0.005-0.02]). Externalizing behavior scores were higher (worse) in children with PAE than in controls (mean [SD], 45.2 [9.0] vs 42.8 [9.0]; mean difference, 2.39 [95% CI, 0.30-4.47]). Several of these regions had significant group-behavior interactions, such that the higher FA was associated with less problematic behaviors in controls (ρ range, −0.24 to −0.08) but no associations were present in the PAE group (ρ range, 0.02-0.16).

Conclusions and Relevance  In this cross-sectional study, children with low levels of PAE had lower FA and more behavioral problems compared with a well-matched control group. These results suggest that PAE, even in small amounts, has a measurable effect on brain structure in children.

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