(1150) Maternal Substance Use And Altered Maternal and Fetal Immune Responses: Implications for Offspring Neurodevelopmental Risk

Maternal substance use (SU) during pregnancy is known to be associated with adverse neurodevelopmental outcomes in offspring, but the mechanisms underlying this risk remain poorly understood. Here we investigated how maternal substance use is associated with altered maternal and fetal immune responses, as potential mediators of developmental risk.


Study Design:

Maternal and cord plasma and peripheral blood mononuclear cells were collected from 68 pregnancies, including N= 17 pregnant women with SU (primarily opioids, marijuana and cocaine, 41% polysubstance use), matched 3:1 to uncomplicated control pregnancies (N=51) for gestational age, maternal pre-pregnancy BMI, and fetal sex. We characterized maternal and fetal T cell phenotypes and cytokine production using flow cytometry. Monocyte function was evaluated after LPS stimulation, and cytokine and chemokine concentrations in maternal and cord plasma were quantified. Maternal and fetal immune activation in SU-exposed cases vs controls was compared using conditional linear regression.


Results:

Increased frequency of pro-inflammatory CD4⁺ and CD8⁺ T cells producing IFN-γ and TNF- was observed in both maternal (Fig 1A) and cord (Fig 1B) blood from SU-exposed pregnancy. Increased levels of pro-inflammatory chemokines and adhesion molecules, such as MCP-1 and ICAM-1, were noted in cord plasma from SU-exposed pregnancies (Fig 1C). Suppressed or exhausted monocyte function was noted in both maternal and cord blood of SU-exposed pregnancies, with reduced capacity to produce IL-6 and MIP-1β upon stimulation (Fig 1D).


Conclusion:

Maternal SU is associated with maternal and fetal T-cell-mediated immune activation, and innate immune exhaustion, consistent with patterns of immune dysregulation previously described in the setting of obesity or viral infection in pregnancy. In the large national HEALthy Brain Child Development study, we will evaluate how maternal and fetal immune dysregulation in the setting of maternal SU may contribute to adverse long-term neurodevelopmental outcomes in children.