Thymectomy Extent, Immune Recovery, and Infectious Burden After Neonatal Cardiac Surgery

Background Neonatal cardiac surgery frequently requires thymectomy, but the consequences of extensive thymic removal remain uncertain. Methods We retrospectively studied 105 neonates undergoing sternotomy (2015–2024), comparing infections and 6‐month lymphocyte recovery after partial versus total thymectomy, with Firth regression adjusted for bypass duration and surgical era. Separate cohorts underwent paired plasma biomarker (n=8) and whole‐blood RNA sequencing (n=4) analysis before and after thymectomy. Results Among 105 neonates, 27 underwent partial and 78 total thymectomy. Multiple infections occurred in 2 of 27 (7%) after partial and 23 of 78 (30%) after total thymectomy (P=0.02); after adjustment for bypass duration and surgical era, the association was not statistically significant (Firth‐adjusted odds ratio, 2.99 [95% CI, 0.82–15.85]; P=0.10). Median lymphocyte count decreased after total but increased after partial thymectomy (change, −0.8 versus +0.9×10 3 /μL; P=0.011). Tumor necrosis factor‐α decreased in all 8 biomarker participants (unadjusted P=0.0078). RNA sequencing in 4 patients (2 partial, 2 total thymectomy) identified 835 differentially expressed genes; pre–T‐cell receptor α decreased in all 4 pairs (log2 fold change, −2.50; adjusted P=6×10 ‐6 ). Conclusions Total thymectomy was associated with reduced 6‐month lymphocyte recovery and higher unadjusted odds of multiple infections. The infection association was not statistically significant after adjustment, and few events (2 of 27 after partial thymectomy) limit precision and cannot exclude a clinically important effect; these findings are hypothesis‐generating. Biomarker and transcriptomic findings are exploratory and cannot distinguish thymectomy from surgery, maturation, or postoperative recovery. Prospective studies are underway to evaluate thymic preservation and autologous reimplantation.