Modulation of Immune Cells by Aspirin During Pregnancy

Pregnancy requires precise maternal immune adaptation to support fetal development while maintaining defense against external threats. Disruption of this balance can result in complications such as preeclampsia (PE), a major cause of maternal and fetal morbidity and mortality. Low-dose aspirin (LDA) is widely used to prevent PE, but its immunomodulatory mechanisms are not fully understood. In this observational study (CES-BS_SF_160_2022; NCT06882850), 32 healthy pregnant women were enrolled and PE risk assessed; 16 classified as high-risk received LDA (150 mg/day) from the first trimester until 36 weeks, and 16 served as controls. Peripheral blood was collected in each trimester (T1, T2, T3), with an additional sample 4 weeks after LDA initiation in the Risk Group (T1.2). Complete blood counts and flow cytometry assessed immune cell populations. Both groups were well-matched for maternal, delivery, and neonatal characteristics, with no significant differences in complications or adverse outcomes. White blood cell subpopulations did not differ significantly. However, the Risk Group had significantly lower haemoglobin and platelet levels in the second trimester. T cell frequencies increased in the Risk Group by the second trimester, with higher percentages of CD4 and CD8 T cells. NK cell analysis showed a decrease in total NK cells at the second trimester versus 4 weeks after LDA initiation, with an increase in CD56^bright (tolerogenic) NK cells and a decrease in CD56^dim (cytotoxic) NK cells. Regulatory T cell (Treg) analysis revealed increased naïve and activated (HLA-DR⁺) Treg cells and decreased memory Treg cells at the second trimester. Activated (HLA-DR⁺) Th17 and Th17.1 cells were lower in the Risk Group at the second trimester. These results suggest that LDA in high-risk pregnancies is associated with lower haemoglobin and platelet levels, an increase in naïve Treg cells, and a shift from cytotoxic to tolerogenic NK cells. The decline in activated Th17 and Th17.1 cells indicates enhanced immune tolerance and reduced inflammation, supporting LDA's role in modulating immune responses to promote healthy pregnancy outcomes. Importantly, these findings should be interpreted as hypothesis-generating; the limited sample size and single-center design constrain the strength of clinical inferences and underscore the need for replication in larger, multicenter cohorts. Further research is needed to determine whether these immunological changes correlate with improved clinical outcomes in broader populations. Trial Registration: ClinicalTrials.gov: NCT06882850.