Diffusion Tensor Imaging of White Matter in Children Born from Preeclamptic Gestations

BACKGROUND AND PURPOSE:Individuals born from pregnancies complicated by preeclampsia have an elevated risk for cognitive impairment. Deviations in maternal plasma angiokines occur for prolonged intervals before clinical signs of preeclampsia. We hypothesized that fetal brain vascular and nervous tissue development become deviated during maternal progression toward preeclampsia and that such deviations would be detectable by MR imaging.MATERIALS AND METHODS:In this pilot study, 10 matched (gestational and current ages) pairs (5 boys/5 girls, 7–10 years of age) from preeclampsia or control pregnancies were examined by using diffusion tensor MR imaging. An unbiased voxel-based analysis was conducted on fractional anisotropy and mean diffusivity parametric maps. Six brain ROIs were identified for subsequent analysis by tractography (middle occipital gyrus, caudate nucleus and precuneus, cerebellum, superior longitudinal fasciculus, and cingulate gyrus).RESULTS:Statistical differences were present between groups for fractional anisotropy in the caudate nucleus (offspring from preeclamptic gestation > controls), volume of the tract for the superior longitudinal fasciculus (offspring from preeclamptic gestation > controls) and the caudate nucleus (offspring from preeclamptic gestation > controls), and for parallel diffusivity of the cingulate gyrus (offspring from preeclamptic gestation > controls).CONCLUSIONS:These novel preliminary results along with previous results from the same children that identified altered cerebral vessel calibers and increased regional brain volumes justify fully powered MR imaging studies to address the impact of preeclampsia on human fetal brain development.

Hypertensive disorders during human pregnancy include acute-onset emergency preeclampsia (PE), seen at a frequency of 2%–8% of all gestations.¹ PE is a systemic vascular inflammatory syndrome occurring between midpregnancy and term and is the leading cause of maternal and fetal morbidity and mortality. Up to 12% of annual maternal deaths² and up to 25% of annual fetal and neonatal deaths globally³ are PE-associated. Leading hypotheses addressing the pathophysiology of PE focus on progressive deficits in uteroplacental angiogenesis and maternal vascular remodeling well before the onset of clinical signs, due to an imbalance in angiokines and soluble angiokine receptors, which are predominantly products of the placenta.⁴A recent systematic review of the impact of maternal hypertension (all forms) during pregnancy on offspring addressed outcomes after 6 months of life. The review identified cardiovascular, immune, metabolic, and behavioral/neurologic effects on individuals born from preeclamptic mothers (PE-F1s). For PE-F1s, lower cognitive function was the prominent, reliable association.⁵ The deficits in cognitive functions reported for PE-F1s^5–7 include lower intelligence quotient scores,^8,9 reduced verbal and nonverbal abilities,^10,11 and reduced arithmetic reasoning.^12,13Recently, we conducted a pilot study to determine whether clinical cognitive function test outcomes and brain MR imaging findings differed between PE-F1s and typical 7- to 10-year-old children.¹⁴ The hypothesis driving this research posits that the progressive dysregulation of angiokines that is clinically associated with maternal PE development reflects conditions occurring not only in placental but also in all fetal tissues and impacts fetal cerebrovascular development. This hypothesis¹⁵ predicts that brain anatomy and function differ between PE-F1s and children born from normotensive mothers due to the use of common molecular pathways during vascular and neuronal cell differentiation (vascular endothelial growth factor pathways) and to the importance of cerebral blood flow for anatomic and functional brain development. Our pilot study suggested specific deficits in cognitive testing and in eye-movement control.¹⁶ Initial volumetric analyses of brain anatomic regions by using high-resolution T1-weighted MR imaging datasets identified 5 regions of anatomic enlargement in PE-F1s (cerebellum, temporal lobe, left amygdala, right amygdala, and brain stem). In addition, reduced vascular radii were identified from time-of-flight MR angiography datasets in the occipital and parietal lobes.¹⁴ These preliminary results were the first reported MR imaging/MRA findings in PE-F1s of any age group.The aim of the current study was to determine whether microstructural properties, including myelination patterns and white matter connectivity analyzed by diffusion tensor MR imaging, differ between PE-F1s and matched typical children. A further goal was to assess whether DTI findings overlapped the previously identified anatomic or vascular deviations in these children.¹⁴