BACKGROUND AND PURPOSE:Pre-eclampsia is a serious clinical gestational disorder occurring in 3%-5% of all human pregnancies and characterized by endothelial dysfunction and vascular complications. Offspring born of pre-eclamptic pregnancies are reported to exhibit deficits in cognitive function, higher incidence of depression, and increased susceptibility to stroke. However, no brain imaging reports exist on these offspring. We aimed to assess brain structural and vascular anatomy in 7-to 10-year-old offspring of pre-eclamptic pregnancies compared with matched controls.

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Prenatal alcohol exposure (PAE) can cause central nervous system dysfunction and widespread structural anomalies as detected by magnetic resonance imaging (MRI). This study focused on diffusion tensor imaging (DTI) of white matter in a large sample of PAE participants that allowed us to examine correlations with behavioral outcomes. Participants were confirmed PAE (n = 69, mean age = 12.5 ± 3.2 years) or typically developing control children (n = 67, mean age = 12.1 ± 3.2 years) who underwent brain MRI, eye movement tasks, and psychometric tests. A semi-automated tractography method extracted fractional anisotropy (FA) and mean diffusivity (MD) values from 15 white matter tracts. The PAE group displayed decreased FA compared with controls in multiple tracts including 3 corpus callosum regions, right corticospinal tract, and 3 left hemisphere tracts connecting to the frontal lobe (cingulum, uncinate fasciculus, and superior longitudinal fasciculus). Significant group by sex interactions were found for the genu, left superior longitudinal fasciculus, and the left uncinate, with females in the PAE group exhibiting lower FA compared with control females. Correlations were found between DTI and eye movement measures in the control group, but these same relationships were absent in the PAE group. In contrast, no correlations were found between DTI and any of the psychometric tests used in this study. These findings support the hypothesis that measures of eye movement control may be valuable functional biomarkers of the brain injury induced by PAE as these tasks reveal group differences that appear to be linked to deficits in white matter integrity in the brain. Hum Brain Mapp 38:444-456, 2017. © 2016 Wiley Periodicals, Inc.

Background: Fetal alcohol spectrum disorders (FASD) is one of the most common causes of developmental disabilities and neurobehavioral deficits. Despite the high-prevalence of FASD, the current diagnostic process is challenging and time- and money- consuming, with underreported profiles of the neurocognitive and neurobehavioral impairments because of limited clinical capacity. We assessed children/youth with FASD from a multimodal perspective and developed a high-performing, low-cost screening protocol using a machine learning framework. Methods and Findings: Participants with FASD and age-matched typically developing controls completed up to six assessments, including saccadic eye movement tasks (prosaccade, antisaccade, and memory-guided saccade), free viewing of videos, psychometric tests, and neuroimaging of the corpus callosum. We comparatively investigated new machine learning methods applied to these data, toward the acquisition of a quantitative signature of the neurodevelopmental deficits, and the development of an objective, high-throughput screening tool to identify children/youth with FASD. Our method provides a comprehensive profile of distinct measures in domains including sensorimotor and visuospatial control, visual perception, attention, inhibition, working memory, academic functions, and brain structure. We also showed that a combination of four to six assessments yields the best FASD vs. control classification accuracy; however, this protocol is expensive and time consuming. We conducted a cost/benefit analysis of the six assessments and developed a high-performing, low-cost screening protocol based on a subset of eye movement and psychometric tests that approached the best result under a range of constraints (time, cost, participant age, required administration, and access to neuroimaging facility). Using insights from the theory of value of information, we proposed an optimal annual screening procedure for children at risk of FASD. Conclusions: We developed a high-capacity, low-cost screening procedure under constrains, with high expected monetary benefit, substantial impact of the referral and diagnostic process, and expected maximized long-term benefits to the tested individuals and to society. This annual screening procedure for children/youth at risk of FASD can be easily and widely deployed for early identification, potentially leading to earlier intervention and treatment. This is crucial for neurodevelopmental disorders, to mitigate the severity of the disorder and/or frequency of secondary comorbidities.

Background: We examined the accuracy and characteristics of saccadic eye movements in children with fetal alcohol spectrum disorder (FASD) compared with typically developing control children. Previous studies have found that children with FASD produce saccades that are quantifiably different from controls. Additionally, animal studies have found sex-based differences for behavioral effects after prenatal alcohol exposure. Therefore, we hypothesized that eye movement measures will show sexually dimorphic results.Methods: Children (aged 5–18 years) with FASD (n = 71) and typically developing controls (n = 113) performed a visually-guided saccade task. Saccade metrics and behavior were analyzed for sex and group differences.Results: Female control participants had greater amplitude saccades than control males or females with FASD. Accuracy was significantly poorer in the FASD group, especially in males, which introduced significantly greater variability in the data. Therefore, we conducted additional analyses including only those trials in which the first saccade successfully reached the target within a ± 1° window. In this restricted amplitude dataset, the females with FASD made saccades with significantly lower velocity and longer duration, whereas the males with FASD did not differ from the control group. Additionally, the mean and peak deceleration were selectively decreased in the females with FASD.Conclusions: These data support the hypothesis that children with FASD exhibit specific deficits in eye movement control and sensory-motor integration associated with cerebellar and/or brain stem circuits. Moreover, prenatal alcohol exposure may have a sexually dimorphic impact on eye movement metrics, with males and females exhibiting differential patterns of deficit.

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These data suggest that children with FASD may have deficits in eye movement control and sensory-motor integration including cerebellar circuits, thereby impairing saccade accuracy.