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Principal Investigator: Kirsty Donald
Organization: UNIVERSITY OF CALIFORNIA LOS ANGELES
Fiscal Year: 2024
Award: $521,003
Funding agency: National Institute on Alcohol Abuse and Alcoholism
Maternal substance use disorders are a substantial public health concern and the neurological consequences
of prenatal exposure are a major threat to the long-term health of offspring. Globally, prevalence of Fetal
Alcohol Syndrome (FAS) and Fetal Alcohol Spectrum Disorders (FASD) is between 2-7 and 20-50 per 1000,
respectively. By contrast, in certain high-risk communities in South Africa, prevalence is reported to be as high
as 63 and 155 per 1000, respectively. Though prenatal alcohol exposure (PAE) is known to affect the central
nervous system, to date, little data exists in respect of the impact of PAE in early childhood and followed
through into adolescence. For neurodevelopmental disorders, studies have consistently shown that early
intervention, based on detection and targeted interventions, leads to better long-term outcomes. We aim to
address this precise gap in knowledge by imaging the brain and 3D face across the FASD continuum
to investigate early biomarkers, trajectories, and functional correlates of PAE in a cohort followed
prospectively from birth to age 12 years. Data: Our cohort includes a highly characterized subsample of
children (PAE and healthy controls) enrolled in the Drakenstein Child Health Study in Cape Town, South
Africa, who have been scanned as neonates, 2-years, and 6 years of age. Preliminary published data shows
highly significant relationships between PAE and regional gray and white matter changes at each of these
timepoints as well as altered white matter maturational trajectories. An additional longitudinal assessment at
12-years will yield a unique FASD sample with 4 distinct time points (infants, toddlers, children and
adolescents), allowing characterization of brain and face morphology and brain structure and function in this
previously understudied full childhood range. This proposal addresses fundamental gaps concerning the
presence, timing and regional specificity of altered brain morphology and structural and functional connectivity
in association with the effects of PAE on the developing brain from birth to 12 years, and the relationships with
facial dysmorphology. The research team has successfully gathered data from the proposed cohort as
neonates, 2–years and 6 years of age. The benefits of extending this research to a subsequent imaging time-
point, with a larger range of developmental and neurobehavioral assessments, provides an unprecedented
opportunity to determine longitudinal effects of PAE on the trajectory of the developing brain in these critical
years through early adolescence, the links between neural and face predictors of PAE and the long-term
clinical significance of these findings. This research will illuminate early neurodevelopmental trajectories
leading to subsequent behavioral and neurological disturbances, which may allow opportunities for targeting
interventions when brain plasticity is still relatively fluid. This project might also lead to new strategies for early
diagnosis using both face and brain biomarkers.
Terms: <0-11 years old><12 year old><12 years of age><12-20 years old><2 year old><2 years of age><3-D><3-Dimensional><3D><6 year old><6 years of age><Address><Adolescence><Adolescent><Adolescent Youth><Affect><Age><Aging><Alcohol Chemical Class><Alcohols><Area><Attention><Behavior><Behavioral><Biological><Biological Markers><Birth><Brain><Brain Mapping><Brain Nervous System><Brain imaging><CNS Nervous System><Central Nervous System><Child><Child Health><Child Youth><Childhood><Children (0-21)><Chronic stress><Cognition><Cognitive><Cohort Studies><Communities><Computing Methodologies><Concurrent Studies><Corpus Striatum><Corpus striatum structure><Corticospinal Tracts><Data><Data Collection><Decision Making><Detection><Development><Dysmorphology><Early Diagnosis><Early Intervention><Encephalon><Enrollment><Environment><Environmental Exposure><FASD><Face><Fetal Alcohol Exposure><Fetal Alcohol Spectrum Disorder><Fetal Alcohol Syndrome><Fetal ETOH Exposure><Fetal Ethanol Exposure><Fetal alcohol effects><Funding><General Population><General Public><Goals><Health><Image><Impulsivity><In Utero Alcohol Exposure><In Utero ETOH Exposure><In Utero Ethanol Exposure><Individual><Infant><Intervention><Intervention Strategies><Joints><Knowledge><Life><Link><Liquid substance><Location><Long-term cohort><Longitudinal cohort><Longterm cohort><Low-resource area><Low-resource community><Low-resource environment><Low-resource region><Low-resource setting><Malnutrition><Measurement><Measures><Mental Health><Mental Hygiene><Methodology><Methods><Modeling><Morphology><Neonatal><Neural Development><Neuraxis><Neurobiology><Neurodevelopmental Disorder><Neurologic><Neurological><Neurological Development Disorder><Nutritional Deficiency><Outcome><Parturition><Pathway interactions><Pattern><Phase><Photography><Population><Prenatal Alcohol Exposure><Prenatal ETOH Exposure><Prenatal Ethanol Exposure><Prevalence><Property><Psychological Health><Public Health><Publishing><Reporting><Research><Resource-constrained area><Resource-constrained community><Resource-constrained environment><Resource-constrained region><Resource-constrained setting><Resource-limited area><Resource-limited community><Resource-limited environment><Resource-limited region><Resource-limited setting><Resource-poor area><Resource-poor community><Resource-poor environment><Resource-poor region><Resource-poor setting><Risk><Sampling><Scanning><Shapes><Societies><South Africa><Specificity><Striate Body><Striatum><Structure><Substance Use Disorder><Surface><Testing><Thalamic structure><Thalamus><Time><Toddler><Undernutrition><Variant><Variation><Youth><Youth 10-21><adolescence (12-20)><adolescent mental health><age 12 years><age 2 years><age 6 years><aged 2 years><aged two years><ages><alcohol exposed><alcohol exposure><alcohol-exposed pregnancy><alcoholic embryopathy><behavior outcome><behavioral outcome><bio-markers><biologic><biologic marker><biomarker><brain abnormalities><brain morphology><brain visualization><clinical significance><clinically significant><cohort><computational methodology><computational methods><computer based method><computer based prediction><computer methods><computing method><cost><developmental><diagnostic approach><diagnostic strategy><dietary deficiency><digital><early adolescence><early biomarkers><early childhood><early detection><early detection biomarkers><early detection markers><embryofetal alcohol syndrome><embryopathia alcoholica><enroll><ethanol exposed><ethanol exposure><executive control><executive function><experience><exposed in utero><exposed to alcohol><exposed to alcohol prenatally><exposed to ethanol><exposure to alcohol><exposure to ethanol><exposure to violence><faces><facial><fetal exposure><flexibility><flexible><fluid><gestation ETOH exposure><gestation alcohol exposure><gestation ethanol exposure><gestational ethanol exposure><gray matter><high risk><imaging><in utero exposure><indexing><interest><intergenerational><interventional strategy><intra-uterine environmental exposure><intrauterine environmental exposure><juvenile><juvenile human><kids><liquid><malnourished><neonate><neural><neural control><neural imaging><neural regulation><neuro-imaging><neurobehavioral><neurobiological><neurodevelopment><neurodevelopmental disease><neuroimaging><neurological imaging><neuromodulation><neuromodulatory><neuroregulation><novel><nutrition deficiency><nutrition deficiency disorder><nutritional deficiency disorder><offspring><pathway><pediatric><predictive modeling><pregnancy ETOH exposure><pregnancy alcohol exposure><pregnancy ethanol exposure><prenatal alcohol effect><prenatal exposure><prenatally alcohol exposed><prenatally exposed><prenatally exposed to alcohol><prospective><psychosocial><resilience><resilient><six year old><six years of age><social><statistics><striatal><substance use><substance use and disorder><substance using><substantia alba><substantia grisea><success><sugar><thalamic><three dimensional><tool><twelve year old><twelve years of age><two year old><two years of age><violence exposure><white matter><white matter change><youngster>