Association Between Prenatal Alcohol Exposure and Craniofacial Shape of Children at 12 Months of Age

Evelyne Muggli, MPH1,2; Harold Matthews, BPsych(Hons)2,3,4; Anthony Penington, MDBS2,3,4; et alPeter Claes, PhD4,5,6; Colleen O’Leary, PhD7; Della Forster, PhD8,9; Susan Donath, MA2,10; Peter J. Anderson, PhD2,11,12; Sharon Lewis, PhD1,2; Cate Nagle, PhD13,14; Jeffrey M. Craig, PhD2,15; Susan M. White, MBBS2,16; Elizabeth J. Elliott, MD17; Jane Halliday, PhD1,2
Author Affiliations
JAMA Pediatr. Published online June 5, 2017.

Key Points

Is there an association between different levels of prenatal alcohol exposure and child craniofacial shape at 12 months?

This cohort study conducted an objective and sensitive craniofacial phenotype analysis of 415 children, which showed an association between prenatal alcohol exposure and craniofacial shape at almost every level of exposure examined. Differences in the midface and nose resemble midface anomalies associated with fetal alcohol spectrum disorder.

Any alcohol consumption has consequences on craniofacial development, supporting advice that complete abstinence from alcohol while pregnant is the safest option; it remains unclear whether the facial differences are associated neurocognitive outcomes of prenatal alcohol exposure.


Children who receive a diagnosis of fetal alcohol spectrum disorder may have a characteristic facial appearance in addition to neurodevelopmental impairment. It is not well understood whether there is a gradient of facial characteristics of children who did not receive a diagnosis of fetal alcohol spectrum disorder but who were exposed to a range of common drinking patterns during pregnancy.

To examine the association between dose, frequency, and timing of prenatal alcohol exposure and craniofacial phenotype in 12-month-old children.

Design, Setting, and Participants
A prospective cohort study was performed from January 1, 2011, to December 30, 2014, among mothers recruited in the first trimester of pregnancy from low-risk, public maternity clinics in metropolitan Melbourne, Australia. A total of 415 white children were included in this analysis of 3-dimensional craniofacial images taken at 12 months of age. Analysis was performed with objective, holistic craniofacial phenotyping using dense surface models of the face and head. Partial least square regression models included covariates known to affect craniofacial shape.

Low, moderate to high, or binge-level alcohol exposure in the first trimester or throughout pregnancy.

Main Outcomes and Measures
Anatomical differences in global and regional craniofacial shape between children of women who abstained from alcohol during pregnancy and children with varying levels of prenatal alcohol exposure.

Of the 415 children in the study (195 girls and 220 boys; mean [SD] age, 363.0 [8.3] days), a consistent association between craniofacial shape and prenatal alcohol exposure was observed at almost any level regardless of whether exposure occurred only in the first trimester or throughout pregnancy. Regions of difference were concentrated around the midface, nose, lips, and eyes. Directional visualization showed that these differences corresponded to general recession of the midface and superior displacement of the nose, especially the tip of the nose, indicating shortening of the nose and upturning of the nose tip. Differences were most pronounced between groups with no exposure and groups with low exposure in the first trimester (forehead), moderate to high exposure in the first trimester (eyes, midface, chin, and parietal region), and binge-level exposure in the first trimester (chin).

Conclusions and Relevance
Prenatal alcohol exposure, even at low levels, can influence craniofacial development. Although the clinical significance of these findings is yet to be determined, they support the conclusion that for women who are or may become pregnant, avoiding alcohol is the safest option.