Low Prenatal Alcohol Exposure Affects Facial Development

Nicola M. Parry, DVM

June 05, 2017

Prenatal alcohol exposure (PAE), even at low levels, is consistently associated with differences in craniofacial shape among affected children, a new study shows. Differences resemble midfacial abnormalities associated with fetal alcohol spectrum disorder (FASD).

Evelyne Muggli, MPH, from the University of Melbourne, Victoria, Australia, and colleagues published the results of their prospective cohort study online June 5 in JAMA Pediatrics.

"A consistent association with craniofacial shape was observed in almost all exposure groups, with differences concentrated on regions around the nose, eyes, upper lips, and lower lips," the authors write.

A diagnosis of fetal alcohol syndrome (FAS) in children is currenty based on characteristic findings of cognitive impairment, growth abnormalities, and distinctive facial features — specifically, small palpebral fissures, a flat philtrum, and a thin upper lip.

A previous study using objective three-dimensional facial imaging showed that facial shape in children with FAS differs from that of children without PAE. In addition, researchers saw differences between the unexposed children and children with partial FAS or heavy alcohol exposure but without a diagnosis of FAS or partial FAS.

To extend these findings, Muggli and colleagues set out to determine any potential association between different patterns of PAE and craniofacial shape. According to the authors, this study is the first to investigate this association using objective, holistic methods of craniofacial phenotyping.

All of the women were recruited early in pregnancy through the population-based longitudinal study Asking Questions About Alcohol in Pregnancy (AQUA). They were recruited between July 2011 and July 2012 from low-risk public maternity clinics in Melbourne, Australia.

The study included 415 white children (195 girls and 220 boys) and analyzed three-dimensional craniofacial images collected from them at 12 months of age.

Alcohol exposure levels were categorized as low (≤20 g of absolute alcohol [AA] per occasion and ≤70 g of AA per week), moderate (21 g to 49 g of AA per occasion and ≤70 g of AA per week), high (>70 g of AA per week), and binge (≥50 g of AA per occasion). Mothers who abstained from drinking alcohol during pregnancy made up the control group for all analyses. Data on alcohol consumption were collected for the 3 months before pregnancy as well as for each trimester of pregnancy.

Of the 326 children with PAE, 193 (59.2%) were exposed throughout pregnancy, while 133 (40.8%) were exposed in the first trimester only.

The researchers found a consistent association between craniofacial shape and PAE at almost any level, regardless of whether exposure occurred only in the first trimester or throughout pregnancy.

Differences in craniofacial shape were prominent around the midface, nose, lips, and eyes. They comprised mild midfacial recession and superior displacement of points of the nose, indicating a shortened nose and upturned nose tip.

Changes were most pronounced between children without PAE and those with low PAE in the first trimester (evident around the forehead), moderate to high PAE in the first trimester (evident around the eyes, midface, chin, and parietal region), and binge-level PAE in the first trimester (evident around the chin).

However, abnormalities were seen even in children with low PAE and in those whose mothers had stopped drinking alcohol in the first trimester, the authors say.

The craniofacial features found in this study indicate mild midfacial recession suggestive of subclinical hypoplasia, and an upturned nasal tip, in children with PAE.

However, the authors stress that because cognitive outcomes for the children included in the study have not yet been evaluated, the diagnostic or predictive value of the study's findings remains unknown.

"Although the clinical significance of our findings is yet to be determined, these findings support the conclusion that, for women who are, or may become pregnant, avoiding alcohol is the safest option," the authors conclude.

In an accompanying editorial, Carol Bower, PhD, from the University of Western Australia, Perth, and Gareth Baynam, PhD, from the Western Australian Register of Developmental Anomalies and Genetic Services of Western Australia, Perth, acknowledge the strengths of the study.

These strengths include the range of PAE examined, from abstinence through high levels of drinking, and the various periods during pregnancy at which alcohol consumption was measured.

According to the editorialists, this study highlights use of facial imaging to potentially improve and simplify the diagnosis of FASD and to reduce the number of false-negative and false-positive diagnoses.

The facial phenotyping performed in this study provides an objective and refined outcome measure, they say. "The associations demonstrated are biologically plausible and may have only been able to be demonstrated using the deep precision of 3-dimensional facial analysis."

Whether these measures are associated with neurodevelopmental impairment in these children remains to be determined, they add.

"[B]ecause the clinical significance of the study by Muggli and colleagues is unproven, at this juncture, both support for further study (with larger samples and an examination of neurodevelopmental outcomes) and

caution against the temptation to extrapolate these findings broadly are warranted," they write.

Although national guidelines in several countries advise women to avoid drinking any alcohol during pregnancy, Dr Bower and Dr Baynam note that this message is often met with resistance, particularly because evidence for harm at low PAE is limited.

However, they draw attention to the development of craniofacial abnormalities in this study even in children with low PAE and in those whose mothers had stopped drinking alcohol in the first trimester.

The results of this study will thus "continue the journey toward more robust evidence for informing health policy," the editorialists conclude.

This study was supported by grants from the Australian National Health and Medical Research Council and the Victorian State Government's Operational Infrastructure Support Program. The authors and editorialists have disclosed no relevant financial relationships.

JAMA Pediatr. Published online June 5, 2017. Abstract, Editorial

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