Maternal immune response during pregnancy and neurodevelopmental outcomes: A longitudinal approach.

Background and Objectives: The neurodevelopment of the offspring is suggested to be influenced by the maternal immune system's responses throughout pregnancy, which in turn is also vulnerable to maternal psychosocial stress conditions. Therefore, our main goal was to investigate whether maternal peripheral immunological biomarkers (IB) during two stages of gestation are associated with distinct neurodevelopmental trajectories in the first two years of life. As a second goal, we also explored the association between maternal distal (childhood) and proximal (gestation) stressful experiences and the immunological markers assessed during pregnancy.
Methods: Maternal childhood trauma, depressive and anxiety symptoms, and peripheral IB (IFNγ, IL-10, IL1β, IL6, IL8, TNFα, EGF, IL13, IL17, IL1Ra and IL4) were measured at baseline (8-16 weeks of pregnancy) and at 30 weeks of pregnancy in 160 women. The participants had the blood samples collected from two randomized clinical trials conducted by the same team and methods in the same community. A Principal Component Analysis (PCA) was implemented to create meaningful composite variables that describe the cytokines joint variation. Finally, linear mixed-effects modeling was used to investigate the influence of inflammatory biomarkers, maternal childhood trauma, anxiety, and depressive symptoms on Bayley's III scores trajectories.
Results: The IB profile during the 3rd trimester of pregnancy predicted the offspring's neurodevelopmental trajectories in the first two years of life. The components derived from PCA were important predictors and captured different immune responses, reflecting both pro- and anti-inflammatory states. Maternal stressful experiences did not correlate with the immunological markers. Although not a reliable predictor alone, maternal psychosocial stress at the 1st trimester of pregnancy interacted with the mother's immune response while predicting the neurodevelopmental scores during the first two years of life.
Conclusions: Our results underscore the importance of the maternal immune response during pregnancy in shaping the neurodevelopmental trajectory of the offspring. Additionally, we observed that the maternal distress at the early stages of pregnancy has an incremental effect on the neurodevelopmental outcome but depends upon the immune response.
Competing Interests: We assure that all procedures from the study “Maternal immune response during pregnancy and neurodevelopmental outcomes: a longitudinal approach” were performed in compliance with relevant laws and institutional guidelines. The present study was approved by the Ethics Committee of the University of São Paulo Medical School (ref: 052/15), the University Hospital of the University of São Paulo, and by the Sao Paulo Municipal Health Department. Signed informed consent was given to participants and their primary caregivers. All methods were performed in accordance with the relevant guidelines and regulations. The study was registered at clinicaltrial.gov (Registration NCT02807818-date: June 21, 2016 and NCT04362098 – date: April 24, 2020). No relevant changes to methods, design or outcomes after trial commencement were made. The full study protocol can be sent upon request.
(© 2024 The Authors.)