Gestational diabetes mellitus, autistic traits and ADHD symptoms in toddlers: Placental inflammatory and oxidative stress cytokines do not play an intermediary role

Abstract

OBJECTIVE\nTo evaluate whether gestational diabetes mellitus (GDM) is associated with increased risks of autistic traits and attention deficit/hyperactivity disorder (ADHD) among offspring and whether placental inflammatory and oxidative stress cytokines play an intermediary role.\n\n\nMETHODS\nBased on a prospective cohort study from China, namely, the Ma anshan Birth Cohort study (MABC), 3260 mother-child pairs were included. Autistic traits and ADHD symptoms among children were assessed at 18 months and 36 months, respectively. The mRNA expression levels of fourteen placental cytokines were determined using PCR. Logistic regression analysis was used to examine the associations between GDM and the risks of autistic traits or ADHD symptoms. Mediation analysis was used to assess the potential mediation effects of certain placental inflammatory factors.\n\n\nRESULTS\nOf the 3260 children, 419 (12.85%) were exposed to GDM. The prevalence rates of autistic traits and ADHD symptoms were 13.86% and 6.4%, respectively. A 48.6% increased risk of autistic traits was observed among offspring born to mothers with GDM [odds ratio (OR)\xa0=\xa01.49, 95% confidence interval (95%CI): 1.11-2.00)], while no significant association was found in terms of ADHD symptoms. There were significant positive associations between GDM and IL-10 expression and between HIF1-α and CRP mRNA expression and a significant negative association between GDM and CD206 mRNA expression. The expression of MCP-1 mRNA was negatively associated with the risk of autistic traits [adjusted OR =\xa00.73 (95%CI: 0.73-0.55)]. The levels of TNF-α were positively associated with the risk of ADHD symptoms [OR =\xa02.11 (95%CI: 1.39-3.21)], while GRP78 was inversely associated with it [OR =\xa00.64 (95%CI: 0.44-0.94)]. However, none of the 14 placental cytokines was involved as a key mediator.\n\n\nCONCLUSION\nOur findings suggest that GDM may act as a risk factor for autistic traits in offspring, while the biological mechanisms may not involve the 14 placental cytokines studied. No significant association between GDM and ADHD symptoms was observed.