Early indices of atypical neurodevelopment with fetal alcohol exposure

Ludmila Bakhireva,  Julia Marie Stephen

First published: 19 September 2018 https://grantome.com/grant/NIH/R01-AA021771-05

University of New Mexico Health Sciences Center, Albuquerque, NM, United States

Abstract

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It is well-established that children with facial dysmorphias characteristic of fetal alcohol syndrome (FAS) have cognitive and behavioral deficits. However, many more children with a history of prenatal ethanol exposure (PAE) also have impaired cognitive processing, even in the absence of facial dysmorphia. The prevalence of this broader phenotype, termed fetal alcohol spectrum disorder (FASD), is at least 10 times greater than FAS and represents greater than 1% of the population. In the absence of the characteristic facial dysmorphia, there are currently no reliable bio-behavioral markers to identify young children with FASD, which often delays intervention until behavioral deficits become apparent in school-aged children.

The long-term goal of our research program is to address the clinical challenge of developing early and reliable indices of PAE in infants so that interventions can be implemented at earlier stages of development. The objective of this current research project is to establish a birth cohort of 132 children using an innovative approach for the assessment of PAE, through the combined use of a novel panel of maternal and infant ethanol biomarkers and validated maternal questionnaires and then to measure neurodevelopment using state-of-the-art magneto- and electro- encephalography (MEG/EEG) and behavioral measures at 6 & 20 months of age to identify early indices of functional brain damage in these children.

The rationale for the proposed work is that earlier identification and intervention lead to better outcomes, and behavioral measures alone have yet to reliably identify children at- risk for the long-term adverse neurobehavioral consequences associated with PAE. Our prior work suggests that a combination of biomarkers and questionnaires will provide the best sensitivity and specificity for confirming 2nd or 3rd-trimester alcohol exposure. Furthermore, based on our prior work in toddlers, we hypothesize that children with PAE will demonstrate delayed or impaired sensorimotor functioning that can be measured with MEG/EEG in infants, and these measures will indicate a broader impact of PAE on brain development corresponding to behavioral deficits.

To test this hypothesis, we will identify neurophysiological indices of sensorimotor deficits in 6- & 20-month-old infants with PAE using simultaneous MEG/EEG and their correspondence to broader behavioral and cognitive deficits. Finally, we will determine the predictive ability of ethanol biomarkers and the battery of neuroimaging and neurobehavioral measures collected at 6 months of age to identify functional brain and behavioral deficits at 20 months of age.

This innovative, prospective study will establish a well-characterized birth cohort using a multi-faceted approach to confirm PAE and will subsequently use a unique multimodal neuroimaging and behavioral testing regimen to identify early indices of atypical brain development in infants. The significance of the proposed research lies in the prospect of establishing a clinical foundation for significant vertical advancement in overcoming the challenge of earlier diagnosis in children with FASD.

Public Health Relevance

In the absence of the distinctive facial characteristics used to diagnose Fetal Alcohol Syndrome, a large majority of prenatal alcohol-exposed (PAE) children are difficult to diagnose with Fetal Alcohol Spectrum Disorder, particularly early in life. This liits the opportunities for early interventions that could diminish the long-term adverse neurobehavioral consequences of PAE. The proposed study will employ a novel screening approach to identify children with PAE at birth coupled with a novel use of non-invasive functional brain imaging measures combined with neurobehavioral assessments in 6- and 20-month-old children to identify functional brain damage associated with PAE.

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