Neurodevelopmental Trajectories Following Prenatal Alcohol Exposure

Prenatal alcohol exposure (PAE) interferes with neurodevelopment. The brain is particularly susceptible to the adverse consequences of prenatal alcohol exposure, and numerous studies have documented changes to brain anatomy and function, as well as consequences for cognition, behavior, and mental health. Studies in typically developing individuals have shown that the brain undergoes dynamic developmental processes over an individual’s lifespan. Furthermore, magnetic resonance imaging (MRI) studies in other neurodevelopmental and psychiatric disorders have shown that their developmental trajectories differ from the typical pattern. Therefore, to understand long-term clinical outcomes of fetal alcohol spectrum disorders (FASD), it is necessary to investigate changes in neurodevelopmental trajectories in this population. Here we review studies that have used MRI to evaluate changes in brain structure and function over time via cross-sectional or longitudinal methods in individuals with PAE. Research demonstrates that individuals with PAE have atypical cortical and white matter microstructural developmental trajectories through childhood and adolescence. More research is needed to understand how factors such as sex and postnatal experiences may further mediate these trajectories. Furthermore, nothing is known about the trajectories beyond young adulthood.

Acute Ethanol Exposure during Synaptogenesis Rapidly Alters Medium Spiny Neuron Morphology and Synaptic Protein Expression in the Dorsal Striatum

Fetal alcohol spectrum disorders are caused by the disruption of normal brain development in utero. The severity and range of symptoms is dictated by both the dosage and timing of ethanol administration, and the resulting developmental processes that are impacted. In order to investigate the effects of an acute, high-dose intoxication event on the development of medium spiny neurons (MSNs) in the striatum, mice were injected with ethanol on P6, and neuronal morphology was assessed after 24 h, or at 1 month or 5 months of age. Data indicate an immediate increase in MSN dendritic length and branching, a rapid decrease in spine number, and increased levels of the synaptic protein PSD-95 as a consequence of this neonatal exposure to ethanol, but these differences do not persist into adulthood. These results demonstrate a rapid neuronal response to ethanol exposure and characterize the dynamic nature of neuronal architecture in the MSNs. Although differences in neuronal branching and spine density induced by ethanol resolve with time, early changes in the caudate/putamen region have a potential impact on the execution of complex motor skills, as well as aspects of long-term learning and addictive behavior.

Zebrafish as a Model for Fetal Alcohol Spectrum Disorders

In this review, we will discuss zebrafish as a model for studying mechanisms of human fetal alcohol spectrum disorders (FASDs). We will overview the studies on FASDs so far and will discuss with specific focus on the mechanisms by which alcohol alters cell migration during the early embryogenesis including blastula, gastrula, and organogenesis stages which later cause morphological defects in the brain and other tissues. FASDs are caused by an elevated alcohol level in the pregnant mother’s body. The symptoms of FASDs include microcephaly, holoprosencephaly, craniofacial abnormalities, and cardiac defects with birth defect in severe cases, and in milder cases, the symptoms lead to developmental and learning disabilities. The transparent zebrafish embryo offers an ideal model system to investigate the genetic, cellular, and organismal responses to alcohol. In the zebrafish, the effects of alcohol were observed in many places during the embryo development from the stem cell gene expression at the blastula/gastrula stage, gastrulation cell movement, morphogenesis of the central nervous system, and neuronal development. The data revealed that ethanol suppresses convergence, extension, and epiboly cell movement at the gastrula stage and cause the failure of normal neural plate formation. Subsequently, other cell movements including neurulation, eye field morphogenesis, and neural crest migration are also suppressed, leading to the malformation of the brain and spinal cord, including microcephaly, cyclopia, spinal bifida, and craniofacial abnormalities. The testing cell migration in zebrafish would provide convenient biomarkers for the toxicity of alcohol and other related chemicals, and investigate the molecular link between the target signaling pathways, following brain development.

Initial Feasibility of the “Families Moving Forward Connect” Mobile Health Intervention for Caregivers of Children With Fetal Alcohol Spectrum Disorders: Mixed Method Evaluation Within a Systematic User-Centered Design Approach

Background Fetal alcohol spectrum disorders (FASD) are prevalent neurodevelopmental conditions. Significant barriers prevent family access to FASD-informed care. To improve accessibility, a scalable mobile health intervention for caregivers of children with FASD is under development. The app, called Families Moving Forward (FMF) Connect, is derived from the FMF Program, a parenting intervention tailored for FASD. FMF Connect has 5 components: Learning Modules, Family Forum, Library, Notebook, and Dashboard. Objective This study assesses the feasibility of FMF Connect intervention prototypes. This includes examining app usage data and evaluating user experience to guide further refinements. Methods Two rounds of beta-testing were conducted as part of a systematic approach to the development and evaluation of FMF Connect: (1) an iOS prototype was tested with 20 caregivers of children (aged 3-17 years) with FASD and 17 providers for the first round (April-May 2019) and (2) iOS and Android prototypes were tested with 25 caregivers and 1 provider for the second round (November-December 2019). After each 6-week trial, focus groups or individual interviews were completed. Usage analytics and thematic analysis were used to address feasibility objectives. Results Across beta-test trials, 84% (38/45) of caregivers and 94% (17/18) of providers installed the FMF Connect app. Technological issues were tracked in real time with updates to address problems and expand app functionalities. On use days, caregivers averaged 20 minutes using the app; most of the time was spent watching videos in Learning Modules. Caregiver engagement with the Learning Modules varied across 5 usage pattern tiers. Overall, 67% (30/45) of caregivers posted at least once in the Family Forum. Interviews were completed by 26 caregivers and 16 providers. App evaluations generally did not differ according to usage pattern tier or demographic characteristics. Globally, app users were very positive, with 2.5 times more positive- than negative-coded segments across participants. Positive evaluations emphasized the benefits of accessible information and practical utility of the app. Informational and video content were described as especially valuable to caregivers. A number of affective and social benefits of the app were identified, aligning well with the caregivers’ stated motivators for app use. Negative evaluations of user experience generally emphasized technical and navigational aspects. Refinements were made on the basis of feedback during the first beta test, which were positively received during the second round. Participants offered many valuable recommendations for continuing app refinement, which is useful in improving user experience. Conclusions The results demonstrate that the FMF Connect intervention is acceptable and feasible for caregivers raising children with FASD. They will guide subsequent app refinement before large-scale randomized testing. This study used a systematic, user-centered design approach for app development and evaluation. The approach used here may illustrate a model that can broadly inform the development of mobile health and digital parenting interventions.