Alcohol-related dysmorphic features as predictors of neurodevelopmental delay in infants and preschool-aged children: results from a birth cohort in Ukraine

• Type of Material: Article
• Authors: Gretchen Bandoli, University of California, San Diego; Claire Coles, Emory University; Julie A Kable, Emory University; Kenneth Lyons Jones, University of California, San Diego; Erin Delker, University of California, San Diego; Wladimir Wertelecki, University of California, San Diego; Lyubov Yevtushok, Liviv National Medical University; Natalya Zymak-Zakutnya, OMNI-Net Ukraine Birth Defects Program; Iryna Granovska, OMNI-Net Ukraine Birth Defects Program; Larysa Plotka, OMNI-Net Ukraine Birth Defects Program; Christina Chambers, University of California, San Diego
• Language: English
• Date: 2022-11-14
• Publisher: John Wiley and Sons
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Research Society on Alcoholism.
• Final Published Version (URL): https://doi.org/10.1111/acer.14966
• Title of Journal or Parent Work: Alcohol, Clinical and Experimental Research
• Volume: 46
• Issue: 12
• Start Page: 2236
• End Page: 2244
• Grant/Funding Information: Research described in this manuscript was supported by Grant #U01AA014835 to Christina Chambers funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the NIH Office of Dietary Supplements (ODS). Gretchen Bandoli is funded by the National Institutes on Alcohol Abuse and Alcoholism (1 K01 AA027811-01).; All or part of this work was done in conjunction with the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), which is funded by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA).
• Keywords: prenatal alcohol exposure; predictive modeling; neurodevelopment; dysmorphology
• Research Categories: Health Sciences, Public Health; Biology, Neuroscience; Health Sciences, Epidemiology

Abstract

Background. Cardinal and non-cardinal dysmorphic features are associated with prenatal alcohol exposure (PAE); however, their association with neurodevelopment is less clear. The objective of this study was to determine whether alcohol-related dysmorphic features predicted neurodevelopmental delay in infants and toddlers. Methods. We analyzed a prospective pregnancy cohort in western Ukraine enrolled between 2008-2014. A dysmorphology exam of body size, 3 cardinal and 14 non-cardinal dysmorphic features was performed at approximately 6-12 months of age. PAE was self-reported and operationalized as absolute ounces of alcohol per day around the time of conception. Neurodevelopment was assessed at 6-12 months with the Bayley Scales of Infant Development-II (BSID-II), and at 3.5-4.5 years of age with the Differential Ability Scales-II, the Child Behavior Checklist, and multiple measures that were used to create an executive functioning factor score. We performed logistic regression to predict children’s neurodevelopment from dysmorphic features, growth measures, sex and PAE. Results. From an analytic sample of 582 unique children, 566 had BSID-II scores in infancy, and 289 completed the preschool battery. Models with all cardinal and non-cardinal dysmorphic features, growth measures, sex and PAE had the best performance compared to models with subsets of those inputs. In general, models had poor performance classifying delays in infancy (AUC <0.7) and acceptable performance on preschool-aged outcomes (AUC ~0.75). When the sample was limited to children with moderate to high PAE, predictive ability improved on preschool-aged outcomes (AUC 0.76-0.89). Sensitivity was relatively low on all models (12-63%), although other metrics of performance were higher. Conclusion. Predictive analysis based on dysmorphic features and measures of growth performed modestly in this sample. As these features are reliably measurable at an earlier age than neurodevelopment, their inclusion in predictive models should be further explored and validated in different settings and populations.