Characterization of Maternal and Fetal Immunity Following in Utero Spina Bifida Repair and Surgery-Induced Preterm Birth.

OBJECTIVE: Fetal surgery (FS) for spina bifida (SB) repair improves infant outcomes; however, spontaneous preterm birth (sPTB) is common. We aimed to evaluate maternal and fetal immune responses following FS for SB repair. METHOD: Pregnant participants undergoing fetoscopic SB repair at 24-26 weeks of gestational age (GA) were prospectively recruited and compared to GA matched low-risk controls. Blood samples were collected at baseline, 2-week post-surgery (POD14), and delivery. Cytokine analysis, flow cytometry, and T cell receptor (TCR) sequencing were performed. RESULTS: sPTB occurred in 5/6 of the FS group (0/6 of controls). Maternal blood in the FS group demonstrated increased alpha-fetoprotein (AFP) and anti-inflammatory IL-1RA at baseline and POD14, increased pro-inflammatory IL-8 only post-operatively, and elevated growth factors throughout. T cell phenotypes following FS revealed reduced TH17 frequency but increased activation receptors on cytotoxic T cells. At delivery, the FS cohort had reduced Th2 and Th17 helper T cells and CD4+ memory T cells, but CD8 T cells still showed increased activation. No TCR expansion was detected post-surgery, suggesting antigen-independent activation. Cord blood in FS repaired neonates had increased AFP, IL-8, IL-1RA. CONCLUSION: Systemic immune changes following FS, particularly T cell maturation and activation, were observed. Further characterization of these mechanisms may help predict and prevent surgery-induced PTB, improving outcomes.