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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: CYSLTR2, NOX1, C1QA, CXCL10, C8A, IL23R. mRNA count significantly correlated with social communication FYI score for CYSLTR2 (Pearson r = 0.46, p = 0.024) and CXCL10 (r = 0.43, p = 0.036) and with sensory regulation score for ALOX5 (r = −0.43, p = 0.038) and MAFK (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.

Abstract Objectives Bronchiolitis is a leading cause of infant hospitalisation in the first year of life, and it preferentially affects infants born to mothers with asthma. Here, we evaluate cord blood granulocytes in infants born to mothers with asthma participating in the Breathing for Life Trial (BLT), to investigate early life determinants of bronchiolitis hospitalisation within the first year of life. Methods Cord blood from 89 participants was collected into EDTA tubes and processed within 6 h of birth. Cells were stained in whole cord blood for eosinophils (CD45+, CD193+, CD16−), and neutrophils (CD45+, CD193−, CD16+). Medical records were reviewed for bronchiolitis hospitalisation in the first 12 months of life. Statistical analyses were conducted using Stata IC16.1. Results Logistic regression adjusted for caesarean section, gestational age, maternal smoking during pregnancy, foetal heart deceleration during labour, and season of birth revealed an association between cord blood eosinophil levels and bronchiolitis hospitalisation in the first 12 months of life with an Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve of 0.943 (aOR = 1.35, P = 0.011). Neutrophils were associated with the risk of bronchiolitis hospitalisation in a univariable logistic regression (OR = 0.93, P = 0.029); however, there was no statistical significance in the adjusted model. Conclusions Higher eosinophil numbers in cord blood were associated with bronchiolitis hospitalisation in the first 12 months in a cohort of infants born to asthmatic mothers. This suggests that susceptibility to bronchiolitis in later life is influenced by the immune cell profile prior to viral infection.