Insights into the Complex Immune Environment During Pregnancy and Association with the Developing Human Connectome.

• In Event: Perinatal Experiences and Brain Development

Abstract

Background: Maternal health and intrauterine exposures during pregnancy play a major role in molding and shaping the health and neurodevelopment of our offspring—one such influence is maternal immune activation (MIA). Animal models have shown MIA affects brain structure, neuronal morphology and function and synaptic and neuronal connectivity and can disrupt regulation of developing neurotransmitter systems in offspring (Vlasova et al, 2021). These models have also shed light on the developing immune system and its long-term consequences (e.g., alterations in cytokine expression, and susceptibility to chronic diseases). In contrast human studies of MIA and its relationship with early brain development are sparse, but increasingly show the complex role of multiple immune markers in later risk for neurodevelopmental conditions in offspring (Han et al, 2021). However, to date, the influence of MIA on newborn brain organization and function has limited research and only exploring a few markers (Spann et al, 2018). Aim: This study proposes an analysis of 46 markers of immune activation from the third trimester of pregnancy to understand potential unique phenotypic profiles and common associations of expressed maternal immune markers during pregnancy with the developing human connectome in healthy pregnancies. Sample: 74 healthy women with singleton pregnancies were recruited and underwent blood draws between 34-37 weeks gestation. Both adaptive (e.g., IgG) and innate (e.g., cytokines and acute phase reactants) totaling 46 markers of maternal immune activation, were collected. In addition, for preliminary analyses of MIA in relation to the newborn brain, we utilized 30 participants with MRIs between the ages of 0-6 months. Findings: A principal component analysis (PCA) identified the first 5 PCs explains ~68% of the variance and the first 10 explains ~83% (top PC is 42.1%). Using the top PC each edge in the connectome was correlated with the immune profiles. There were several regions that trended towards significance – one survived correction. This one identified cluster included 359 edges. Summary: To our knowledge this is the first study beginning to observe the influence of 46 maternal immune markers on the developing human connectome. Above we have identified a profile of immune expression. We see multiple areas of the developing human connectome are influenced by MIA during the 3rd trimester of pregnancy. The highest number of edges was observed in the inferior parietal lobe of the left hemisphere – a region associated with functions from basic attention to language and social cognition. Suggesting, deviations in offspring exposure to MIA will longitudinally impact offspring behaviour in these areas essential for human interaction. Next steps: Analysis will be continued on the larger sample of 74 MRIs, exploring the influence of MIA on the developing human connectome with a focus on both the adaptive and innate immune profiles. Implications: This is the first step in providing a blueprint for future longitudinal studies to understand how interruptions (such as MIA) during this period map onto later development and diagnosis of neurodevelopmental conditions. Identification of alterations, critical windows and long-term outcomes could lead to the development of preventative and mechanism-based healthcare, facilitate timely referral for appropriate interventions and provide family support.

Authors

• Ezra Aydin, Columbia University
  Presenting Author

• Raimundo Rodriguez, Yale University School of Medicine

• Catherine Monk, Columbia University Irving Medical Center

• Thirsten Stockton, Columbia University Vagelos College of Physicians and Surgeons

• Bradley S. Peterson, Children’s Hospital Los Angeles

• Dustin Scheinost, Yale School of Medicine

• Marisa N. Spann, Columbia University