Prenatal diagnosis · 2025
Characterization of Maternal and Fetal Immunity Following in Utero Spina Bifida Repair and Surgery-Induced Preterm Birth.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Martinez Carmona Katherine, Lothert Petra K, Fedyshyn Bohdana, Jang Jin Sung, Govindan Aparna, Pacora Portella Percy N, Lemens Maureen A, Chakraborty Rana, Ruano Rodrigo, Peiro Jose L, Bergh Eric P, Schenone Mauro H, Enninga Elizabeth Ann L
Аннотация
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.
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.