Brain Volume in Fetal Alcohol Spectrum Disorders Over a 20-Year Span

Abstract

ImportanceAnomalous brain development and mental health problems are prevalent in fetal alcohol spectrum disorders (FASD), but there is a paucity of longitudinal brain imaging research into adulthood. This study presents long-term follow-up of brain volumetrics in a cohort of participants with FASD.ObjectiveTo test whether brain tissue declines faster with aging in individuals with FASD compared with control participants.Design, Setting, and ParticipantsThis cohort study used magnetic resonance imaging (MRI) data collected from individuals with FASD and control individuals (age 13-37 years at first magnetic resonance imaging [MRI1] acquired 1997-2000) compared with data collected 20 years later (MRI2; 2018-2021). Participants were recruited for MRI1 through the University of Washington Fetal Alcohol Syndrome (FAS) Follow-Up Study. For MRI2, former participants were recruited by the University of Washington Fetal Alcohol and Drug Unit. Data were analyzed from October 2022 to August 2023.Main Outcomes and MeasuresIntracranial volume (ICV) and regional cortical and cerebellar gray matter, white matter, and cerebrospinal fluid volumes were quantified automatically and analyzed, with group and sex as between-participant factors and age as a within-participant variable.ResultsOf 174 individuals with MRI1 data, 48 refused participation, 36 were unavailable, and 24 could not be located. The remaining 66 individuals (37.9%) were rescanned for MRI2, including 26 controls, 18 individuals with nondysmorphic heavily exposed fetal alcohol effects (FAE; diagnosed prior to MRI1), and 22 individuals with FAS. Mean (SD) age was 22.9 (5.6) years at MRI1 and 44.7 (6.5) years at MRI2, and 35 participants (53%) were male. The FAE and FAS groups exhibited enduring stepped volume deficits at MRI1 and MRI2; volumes among control participants were greater than among participants with FAE, which were greater than volumes among participants with FAS (eg, mean [SD] ICV: control, 1462.3 [119.3] cc at MRI1 and 1465.4 [129.4] cc at MRI2; FAE, 1375.6 [134.1] cc at MRI1 and 1371.7 [120.3] cc at MRI2; FAS, 1297.3 [163.0] cc at MRI1 and 1292.7 [172.1] cc at MRI2), without diagnosis-by-age interactions. Despite these persistent volume deficits, the FAE participants and FAS participants showed patterns of neurodevelopment within reference ranges: increase in white matter and decrease in gray matter of the cortex and decrease in white matter and increase in gray matter of the cerebellum.Conclusions and RelevanceThe findings of this cohort study support a nonaccelerating enduring, brain structural dysmorphic spectrum following prenatal alcohol exposure and a diagnostic distinction based on the degree of dysmorphia. FASD was not a progressive brain structural disorder by middle age, but whether accelerated decline occurs in later years remains to be determined.

Biomarkers of Affective Dysregulation Associated with In Utero Exposure to EtOH

“…Systemic treatment with a caspase inhibitor prevented both the dendritic spine pruning and the physiological deficit of LTD without interfering with the ongoing dopaminergic degeneration (discussed in [ 120 ]). In the present study, the increased levels of activated caspase-3 demonstrated in synaptosomes from EtOH-exposed fetuses are consistent with the known loss of brain volume and the cognitive disabilities of children with FAS [ 121 ] and the loss of dendritic spines previously shown in animal fetuses exposed to EtOH [ 122 , 123 ] and in human FAS [ 116 ]. Whether this involves monoaminergic neurons remains to be determined.…”

Expression of placental CD146 is dysregulated by prenatal alcohol exposure and contributes in cortical vasculature development and positioning of vessel-associated oligodendrocytes

“…Regarding sex differences, previous pre-clinical studies reported that the alcohol-induced neurovascular alterations impacting GABAergic interneurons (Léger et al, 2020a) or oligodendrocytes (Brosolo et al, 2022) were not significantly different between males and females. These sex-independent results regarding molecular data have also been observed in human neuroanatomical studies (Fraize et al, 2023;Pfefferbaum et al, 2023). However, they also clearly differ from clinical studies that reported sex-differences regarding alcohol-induced neurodevelopmental disorders (Flannigan et al, 2023).…”