UC San Diego

Background

In animal models, it is possible to induce different alcohol-related dysmorphic abnormalities based on the timing of prenatal alcohol exposure (PAE). Our objective was to assess whether patterns of PAE differentially predict alcohol-related dysmorphic features in 415 infants.

Methods

We analyzed a prospective pregnancy cohort in western Ukraine enrolled between 2008 and 2014. Five distinct trajectories were previously identified to summarize PAE: (i) minimal/no PAE (n = 253), (ii) low/moderate PAE with reduction early in gestation (n = 78), (iii) low/moderate sustained PAE (n = 20), (iv) moderate/high PAE with reduction early in gestation (n = 45), and (v) high sustained PAE (n = 19). A dysmorphology examination of body size, 3 cardinal, and 15 noncardinal dysmorphic features was performed at approximately 6 to 12 months of age. A modified dysmorphology score was created based on previously published weights. Univariate comparisons were made between each dysmorphic feature and trajectory group. Features that differed by trajectory group were assessed in multivariable analyses. Models were adjusted for maternal age, prenatal vitamin use, socioeconomic status, smoking, and child's age at dysmorphology examination, with censoring weights for losses to follow-up.

Results

The 3 highest trajectories predicted total dysmorphology score, with larger effects in sustained exposure groups. Cardinal features: The 3 highest trajectories were each associated with a 2- to 3-fold increased risk of having 2 + cardinal facial features. When assessed individually, there were no consistent associations between the individual trajectories and each cardinal feature. Noncardinal features: The 3 highest trajectories were associated with increased risk of hypotelorism. Only the highest trajectory was associated with heart murmur. The highest trajectory predicted <10th centile for sex and age on height, weight, and head circumference; and moderate/high with reduction trajectory also predicted height.

Conclusions

While we did not observe differential results based on specific trajectories of exposure, findings support the wide range of dysmorphic features associated with PAE, particularly at high and sustained levels.