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Dysmorphological and Neuropsychological Phenotypes of Prenatally Alcohol-Exposed 6-Year-Old Children: A Prospective Longitudinal Birth Cohort Study
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DOI：10.1111/acer.70320.png)
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Abstract
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Background Prenatal alcohol exposure (PAE) disrupts embryonic development, resulting in variable fetal alcohol spectrum disorder (FASD) phenotypes characterized by dysmorphological and neurodevelopmental abnormalities. To elucidate the etiology of FASD, we established a prenatally recruited prospective birth cohort collecting biological samples at birth and longitudinal data from alcohol-exposed and unexposed control children. Methods Dysmorphological, neuropediatric, and neuropsychological assessments were performed at 6 years of age in 28 children with substantial PAE and 52 control children. Results Among the PAE group, 76% (19/25) of the children who completed the full evaluation met the diagnostic criteria for FASD, including five with fetal alcohol syndrome (FAS), six with partial FAS, seven with alcohol-related neurodevelopmental disorder, and one with alcohol-related birth defect. None of the tested children had a prior FASD diagnosis. In addition to the characteristic features of FAS, including short palpebral fissures, smooth philtrum, and thin vermilion border, several additional anomalies, such as mild midface hypoplasia, were significantly associated with PAE (p < 0.001). Also, PAE was associated with both underweight and overweight at 6 years of age, particularly among boys. Neurocognitive assessments revealed lower performance scores and a high prevalence of ADHD symptoms in PAE children compared with controls. Furthermore, PAE children exhibited additional phenotypic features not captured by the diagnostic FASD criteria, including impairments in adaptive and social functioning, somatic health problems, and reduced postural stability. Moreover, 11 children with early-only PAE limited to the first seven gestational weeks showed dysmorphic features and cognitive outcomes comparable to those of children with longer exposure. Conclusions The high proportion of affected children demonstrates the need for systematic follow-up of those with PAE and comprehensive phenotypic characterization to improve FASD identification. Importantly, these findings indicate that substantial PAE limited to very early pregnancy is sufficient to result in FASD with clinically significant neurocognitive impairment.
Keywords:
balance
cognition
dysmorphism
early exposure
fetal alcohol spectrum disorder
prenatal alcohol exposure
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