Autism likelihood in infants born to mothers with asthma is associated with blood inflammatory gene biomarkers in pregnancy

Mothers with asthma or atopy have a higher likelihood of having autistic children, with maternal immune activation in pregnancy implicated as a mechanism. This study aimed to determine, in a prospective cohort of mothers with asthma and their infants, whether inflammatory gene expression in pregnancy is associated with likelihood of future autism. Mothers with asthma were recruited to the Breathing for Life Trial. RNA was extracted from blood samples collected at mid-pregnancy. 300 ng total RNA was hybridized with the nCounter Human Inflammation gene expression panel (Nanostring Technologies, 249 inflammation-related genes). Parents completed the First Year Inventory (FYI) at 12-month follow-up, which assessed an infant's likelihood for autism across 2 behavioural domains: social communication and sensory regulation. A total score ≥19.2 indicated increased likelihood for future autism. Inflammatory gene expression was profiled from 24 mothers: four infants scored in the high autism likelihood range; 20 scored in the low autism likelihood range. Six inflammatory genes were differentially expressed and significantly up-regulated in the high autism likelihood group: <i>CYSLTR2</i>, <i>NOX1</i>, <i>C1QA</i>, <i>CXCL10</i>, <i>C8A</i>, <i>IL23R</i>. mRNA count significantly correlated with social communication FYI score for <i>CYSLTR2</i> (Pearson r = 0.46, p = 0.024) and <i>CXCL10</i> (r = 0.43, p = 0.036) and with sensory regulation score for <i>ALOX5</i> (r = -0.43, p = 0.038) and <i>MAFK</i> (r = -0.46, p = 0.022). In this proof-of-concept study, inflammatory gene expression during pregnancy in mothers with asthma was associated with an infant's likelihood of future autism as well as scores relating to social communication and sensory regulation.