Volumetric cerebral characteristics of children exposed to opiates and other substances in utero

Abstract

Morphometric cerebral characteristics were studied in children with prenatal poly-substance exposure (n=14) compared to controls (n=14) without such exposure. Ten of the substance-exposed children were born to mothers who used opiates (heroin) throughout the pregnancy. Groups were compared across 16 brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, lateral ventricles, inferior lateral ventricles, and the 3rd and 4th ventricles. In addition, continuous measurement of thickness across the entire cortical mantle was performed. Volumetric characteristics were correlated with ability and questionnaire assessments 2 years prior to scan. Compared to controls, the substance-exposed children had smaller intracranial and brain volumes, including smaller cerebral cortex, amygdala, accumbens area, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, and inferior lateral ventricles, and thinner cortex of the right anterior cingulate and lateral orbitofrontal cortex. Pallidum and putamen appeared especially reduced in the subgroup exposed to opiates. Only volumes of the right anterior cingulate, the right lateral orbitofrontal cortex and the accumbens area, showed some association with ability and questionnaire measures. The sample studied is rare and hence small, so conclusions cannot be drawn with certainty. Morphometric group differences were observed, but associations with previous behavioral assessment were generally weak. Some of the volumetric differences, particularly thinner cortex in part of the right lateral orbitofrontal cortex, may be moderately involved in cognitive and behavioral difficulties more frequently experienced by opiate and poly-substance-exposed children.

Figure 1

A sample of the automated segmentation of the brain volumes of two healthy 10 year old boys. Bottom: normal control. Top: opiate exposed. Voxel size is 1 mm³.

Figure 2

Volume distributions measured in number of voxels (mm³, y-axis) and plotted according to age (x-axis) for the different groups with exposure type and risk factors indicated. The lines indicate group means for all exposed children together and controls, respectively.

Figure 3

Partial eta squares plotted for comparison of effect sizes of group when the effect of age at scan, gestational age at birth, and gender is controlled for. ANOVAS were performed for all controls (n = 14) compared to A) all substance exposed (n = 14, df = 1, 23), B) opiate exposed only (n =10, df = 1,19), C) opiate exposed without MMC or AS (n = 8, df = 1, 17).

Figure 4

Results of a general linear model depicting the effect of exposure group on the cortical mantle when the effects of gender, age at scan and gestational age at birth were regressed out. Results are shown for group differences between controls and A) all exposed children, and B) opiate exposed children only.

Figure 5

The scatterplots illustrate the effects of different combination of regressors on cortical thickness in the right hemisphere. The effects are projected onto an inflated brain (left: lateral view, right: medial view). Since there are several possible confounds that correlate with the primary variable of interest (prenatal exposure to opiates), the general linear model approach was repeated systematically with different variables regressed out. As can be seen, the effects are as strong when only the opiate exposed children are included as when all the exposed children are included, even though the sample size is smaller (10 vs. 14 exposed). Further, it can be seen that the effects in parts of the right anterior cingulate and lateral orbitofrontal cortex survive control for a number of possible confounds.

Figure 6

Scatterplots showing the mean thickness of the cerebral cortex in two specific frontal brain areas: a part of anterior cingulate cortex and a part of the lateral orbitofrontal cortex in the right hemisphere. The areas are manually drawn on an inflated brain, which makes it possible to see inside the sulci of the brain surface. The lines represent the mean thickness in the two areas for the each of the two groups.