Exposure to prenatal maternal distress and infant white matter neurodevelopment

Abstract

The prenatal period represents a critical time for brain growth and development. These rapid neurological advances render the fetus susceptible to various influences with life-long implications for mental health. Maternal distress signals are a dominant early life influence, contributing to birth outcomes and risk for offspring psychopathology. This prospective longitudinal study evaluated the association between prenatal maternal distress and infant white matter microstructure. Participants included a racially and socioeconomically diverse sample of 85 mother-infant dyads. Prenatal distress was assessed at 17 and 29 weeks' gestational age (GA). Infant structural data were collected via diffusion tensor imaging at 42-45 weeks' postconceptional age. Findings demonstrated that higher prenatal maternal distress at 29 weeks' GA was associated with increased fractional anisotropy (b = .283, t(64) = 2.319, p = .024) and with increased axial diffusivity (b = .254, t(64) = 2.067, p = .043) within the right anterior cingulate white matter tract. No other significant associations were found with prenatal distress exposure and tract fractional anisotropy or axial diffusivity at 29 weeks' GA, nor earlier in gestation.

Keywords: anxiety; diffusion tensor imaging (DTI); magnetic resonance imaging (MRI); pregnancy; white matter microstructure.

Appendix Figure 1.

Regional averaging along the BNST-Amygdala (left panel) and Cingulum Gyrus (CGC) (right panel) white matter tracts (A) The arc length (red-to-blue colormap) along each fiber tract is defined by setting the central plane of each fiber to 0 (dashed line). (B) Fractional anisotropy (FA) measurements are sampled at regular points along each fiber’s arc length. Colored Plots: FA profile for individual subjects; Black Plot: Mean FA profile averaged over all subjects. The region for the final analyses of each fiber tract (black arc in A) is selected based on the FA profile and the fiber anatomy. (C) Cropped fiber tract profiles used in the final analyses to calculate average tract FA (top panel), AD (bottom panel), MD, and RD. White: Subject FA profiles removed from all further analyses. These profiles exhibit a correlation < 0.5 with the mean FA profile (black plot) along the selected region of interest.

Figure 1.. Model of intergenerational transmission of risk.

The prenatal period is a time when the fetal brain is highly susceptible to the effects of prenatal maternal depression and other signals of maternal psychological and physiological distress. However, the influence of prenatal depression exposure on neonatal neural circuit maturation remains poorly understood. Alterations in the neurodevelopment of white matter microstructure is one potential etiological mechanism through which prenatal stress influences child outcomes.

Figure 2.. Diffusion tensor metrics are calculated along select white matter tracts.

(A) White matter fiber tracts analyzed in the current study. Top: red = uncinate (UNC); yellow = genu of corpus callosum (genu); light blue = inferior fronto-occipital fasciculus (IFOF). Bottom: purple = bed nucleus of the stria terminalis amygdala (BNST); blue = fornix (FNX); green = cingulum hippocampal part (CGH); orange = cingulum gyrus part (CGC) (i.e., anterior cingulum); (B) sagittal (left) and axial (right) view of the fractional anisotropy (FA) (top) and axial diffusivity (AD) (bottom) calculated for a single subject.

Figure 3.. STAI at 29 weeks’ GA and Right Anterior Cingulate Tract.

Maternal distress is associated with increased (A) fractional anisotropy (FA) and (B) increased axial diffusivity (AD). Residuals plotted after accounting for biological sex at birth, postconceptional age, and motion.