Mothers who use cannabis during pregnancy risk disrupting immune gene networks in the placenta and potentially increasing the risk of anxiety and hyperactivity in their children.
These findings emerged from a study led by Yasmin Hurd, PhD, a professor of psychiatry and director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai, New York, and Yoko Nomura, PhD, a professor of behavioural neuroscience at Queen’s College, City University of New York, that was published online in Proceedings of the National Academy of Sciences.
The analysis assessed the effects of gestational maternal cannabis use on psychosocial and physiological measures in young children as well as its potentially immunomodulatory effect on the in utero environment as reflected in the placental transcriptome.
Participants were drawn from a larger cohort in a study launched in 2012; the investigators evaluated offspring aged 3-6 years for hair hormone levels, neuro-behavioural traits on the Behavioural Assessment System for Children survey, and heart rate variability (HRV) at rest and during auditory startle.
The cohort consisted of 322 mother-child dyads and children with prenatal exposure to cannabis were compared with those having no exposure. The cohort consisted of 251 non–cannabis-using mothers and 71 cannabis-using mothers, with mean maternal ages in the two groups of 28.46 years and 25.91 years, respectively. The mothers gave birth at Mount Sinai and they and their children were assessed annually at affiliated medical centers in Mount Sinai’s catchment area.
For a subset of children with behavioural assessments, placental specimens collected at birth were processed for RNA sequencing.
Among the findings:
· Maternal cannabis use was associated with reduced maternal and paternal age, more single-mother pregnancies, state anxiety, trait anxiety, depression, and cigarette smoking.
· Hair hormone analysis revealed increased cortisol levels in the children of cannabis-using mothers, and was associated with greater anxiety, aggression, and hyperactivity.
· Affected children showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone.
In the placenta, there was reduced expression of many genes involved in immune system function. These included genes for type I interferon, neutrophil, and cytokine-signaling pathways.
Several of these genes organized into co-expression networks that correlated with child anxiety and hyperactivity.
The principal active component of cannabis, tetrahydrocannabinol (THC), targets the endocannabinoid system in placental tissue and the developing brain, the authors noted. Exposure during pregnancy is associated with a range of adverse outcomes from foetal growth restriction to low birth weight and preterm birth.
“There are cannabinoid receptors on immune cells, and it is known that cannabinoids can alter immune function, which is important for maintaining maternal tolerance and protecting the foetus,” Hurd said.
“It’s not surprising that something that affects the immune cells can have an impact on the developing foetus.”
“Overall, our findings reveal a relationship between [maternal cannabis use] and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood,” Hurd and colleagues wrote, adding that the results have significant implications for defining mental health issues in the children gestated by cannabis-smoking mothers.
REFERENCE: Rompala et al: Maternal cannabis use is associated with suppression of immune gene networks in placenta and increased anxiety phenotypes in offspring; https://www.pnas.org/content/118/47/e2106115118