A population-based cohort study has found that low to moderate prenatal alcohol exposure may be associated with subtle but distinct facial shape variations in children aged 6 to 8 years. 

In the study, published in JAMA Pediatrics, researchers noted that these differences persisted beyond infancy but did not match the characteristic facial features of fetal alcohol spectrum disorder (FASD). They analyzed 549 children who participated in the AQUA study, a Melbourne-based cohort. Three-dimensional craniofacial imaging was conducted at 12 months and again at 6 to 8 years to compare children with and without prenatal alcohol exposure (PAE):

• 421 children were analyzed at 12 months (336 with PAE).
• 363 children were analyzed at 6 to 8 years (260 with PAE).
• 235 children contributed images at both time points.

PAE was categorized by trimester and frequency, distinguishing between first trimester–only exposure and continued exposure throughout pregnancy. PAE was linked to distinct facial shape changes at both time points:

• Eye shape differences: response-based imputed predicter (RIP) partial Spearman ρ = 0.19 (95% confidence interval [CI] = 0.10–0.29, P < .001)
• Nasal shape differences: RIP partial Spearman ρ = 0.19 (95% CI = 0.09–0.27, P < .001).

Children exposed throughout pregnancy showed similar facial variations as those with first trimester–only exposure. However, no linear dose–response relationship was found, suggesting factors beyond total alcohol intake may influence these changes.

"A linear association between the level of PAE and variation in facial shape was not supported, most likely due to a complex association between PAE dose and timing and the many molecular pathways affected by alcohol," said Evelyne Muggli, MPH, of the Murdoch Children’s Research Institute in Victoria, Australia, and her colleagues.

Though these changes were not diagnostic of FASD, the findings reinforced the potential impact of even low-level prenatal alcohol exposure on craniofacial development. Future studies are needed to explore whether these differences correlate with neurodevelopmental outcomes, brain structure, or cognitive function.

The study focused on children of European descent to control for genetic variability, which may have limited generalizability. Neurodevelopmental assessments at 6 to 8 years did not show measurable deficits, warranting further investigation into the significance of these facial changes.

The study was funded by the National Health and Medical Research Council, with no significant conflicts of interest reported.