Dysmorphological and neuropsychological phenotypes of prenatally alcohol-exposed six-year-old children

Prenatal alcohol exposure (PAE) affects embryonic development, leading to a variable fetal alcohol spectrum disorder (FASD) phenotype with neuronal and dysmorphological defects. To understand the etiology of FASD, we have established a cohort consisting of biological samples at birth and developmental information of prenatally alcohol-exposed and unexposed control children. To explore the phenotypic effects of PAE, we performed neuropsychological, neuropediatric, and dysmorphological assessments on the first 28 PAE children and 52 control children at the age of six. In the PAE group, 76% (19/25) of the children, who attended a full evaluation, met the criteria for FASD at this age. These diagnoses included five children with fetal alcohol syndrome (FAS), six with partial FAS, seven with alcohol-related neurodevelopmental disorder (ARND), and one with alcohol-related birth defect. In addition to characteristic features of FAS, including short palpebral fissure length, smooth philtrum, and thin vermilion (P<0.0001 for each), numerous other anomalies, such as mild midface hypoplasia (P<0.0001), were associated significantly with PAE. Unexpectedly, PAE was associated not only with underweight but also with an increased risk of overweight among six-year-olds, prominently among boys. Neurocognitive assessments indicated lower performance scores and a high prevalence of ADHD symptoms in PAE children compared to controls. Furthermore, additional PAE-associated phenotypic features, such as perturbations in adaptive and social functioning, somatic health issues, as well as reduced postural stability and lower performance in static balance tasks, were observed, which are not included in the diagnostic criteria of FASD. These findings underscore the complexity of FASD diagnosis and the importance of comprehensive phenotypic characterization to improve identification of FASD. This emphasizes the significance of the chosen diagnostic method and may leave some of the tested children without a diagnosis needed for developmental support. Interestingly, early alcohol exposure, up to the seventh gestational week, resulted in similar rates of dysmorphic features and cognitive scores compared to the longer exposure group. These results, along with several ARND diagnoses in the early PAE group, emphasize the vulnerability of early pregnancy to alcohol exposure, particularly the sensitivity of the nervous system. This is also consistent with the guidelines recommending the use of contraception when consuming alcohol and advising individuals to stop drinking alcohol when planning a pregnancy.