Prenatal cocaine effects on brain structure in early infancy

Abstract

Prenatal cocaine exposure (PCE) is related to subtle deficits in cognitive and behavioral function in infancy, childhood and adolescence. Very little is known about the effects of in utero PCE on early brain development that may contribute to these impairments. The purpose of this study was to examine brain structural differences in infants with and without PCE. We conducted MRI scans of newborns (mean age = 5 weeks) to determine cocaine's impact on early brain structural development. Subjects were three groups of infants: 33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine. Infants with PCE exhibited lesser total gray matter (GM) volume and greater total cerebral spinal fluid (CSF) volume compared with controls and infants with non-cocaine drug exposure. Analysis of regional volumes revealed that whole brain GM differences were driven primarily by lesser GM in prefrontal and frontal brain regions in infants with PCE, while more posterior regions (parietal, occipital) did not differ across groups. Greater CSF volumes in PCE infants were present in prefrontal, frontal and parietal but not occipital regions. Greatest differences (GM reduction, CSF enlargement) in PCE infants were observed in dorsal prefrontal cortex. Results suggest that PCE is associated with structural deficits in neonatal cortical gray matter, specifically in prefrontal and frontal regions involved in executive function and inhibitory control. Longitudinal study is required to determine whether these early differences persist and contribute to deficits in cognitive functions and enhanced risk for drug abuse seen at school age and in later life.

Keywords: CSF enlargement; Cortical gray matter; Infant brain development; Magnetic resonance imaging; Prenatal cocaine; Prenatal substance abuse.

Figure 1

A–C, Representative subject’s coronal views of T₁-weighted (A) and T₂-weighted (B) neonatal images which have been automatically segmented (C) into CSF (blue), gray matter (red) and white matter (green). Right brain is on readers’ left. D, Template of the neonatal brain for automatic parcellation into cortical regions (left and right, dorsal and ventral, prefrontal (PF), frontal (FR), parietal (PA) and occipital (OC) regions. E–G, 3-D visualizations of segmented white matter (E, red) and gray matter (F, green), and of CSF shown on the brain cavity surface (G, blue) from the same subject shown in Figure 1A–B.

Figure 2

Regional gray matter (GM) and cerebral spinal fluid (CSF) volume (mm³) differences between cocaine-exposed infants (PCE) compared with (A) drug-free Controls and (B) infants with non-cocaine other drug exposures (NCOC). The left column illustrates significance maps based on p values of ANCOVA comparisons of GM and CSF parcellation volumes depicted in Figure 1F and G. Color scale columns at right depict % difference between group means. Greater blue intensity signifies greater increases in tissue volume in the Cocaine-exposed group; greater yellow intensity denotes greater deficits in the Cocaine-exposed group.