Plasma miRNAs in early childhood indicate prenatal alcohol exposure-associated neurodevelopmental delay

Abstract

Fetal Alcohol Spectrum Disorders (FASDs) are common but require difficult-to-find multi-disciplinary teams for diagnosis. Consequently, a majority of children born with prenatal alcohol exposure (PAE) are never diagnosed and are at risk for adverse secondary outcomes. To address this deficit, we and other groups have searched for biomarkers that either reflect PAE or predict FASD. Plasma miRNAs were previously shown to be biomarkers for both PAE and FASD-associated child outcomes in maternal and neonate/infant plasma samples. The aim of this study was to identify miRNA signatures of atypical development in early childhood (3.1 ± 1.5 years old, range 1.7–8.9 years of age) related to FASD outcomes. miRNAs were assessed from purity-validated plasma samples, using low-density qRT-PCR arrays. Analysis of expressed miRNAs showed that 16 miRNAs were associated with neurodevelopment status, while only 3 were associated with PAE status. Child sex was a critical modifier of altered miRNA profiles, particularly for neurodevelopment status. We identified 7.3-times as many miRNAs associated with atypical neurodevelopment in female compared to male children. Groups of miRNAs and clinical variables were identified that were associated with cognitive performance in both infancy (~ 6 or ~12 month Bayley Scales of Infant Development) and early childhood (Differential Ability Scales-II), with a subset of miRNAs, namely miR-409-3p and let-7 family members, present in multiple models. Critically, model variables explained up to 24–41% of the variance in neurocognitive scores. Childhood plasma miRNAs are indicative of neurodevelopmental outcomes and can contribute to improving risk stratification for children with PAE.