Children with 22q11 Microdeletion Syndrome More Frequently Experience Morbidity After Repair of Tetralogy of Fallot Compared to Children with Trisomy 21

Background: 22q11.2 microdeletion syndrome (22q11) and trisomy 21 (T21) are frequently associated with tetralogy of Fallot (TOF), but it is not known if one syndrome fares differently than the other after complete repair. We hypothesized that postoperative length of stay (LOS) and occurrence of postoperative interventions after complete TOF repair differ between infants with 22q11 versus T21.

Methods: Using the Pediatric Health Information System, we performed a multicenter retrospective cohort study of patients 12 months of age or younger who underwent complete repair of TOF from 2004 to 2019. Three groups were identified based on International Classification of Disease codes: 22q11, T21, and controls (those without a coded genetic syndrome). The outcomes of interest were postoperative LOS and postoperative reintervention, defined as the postoperative occurrence of one or more of the following: tracheostomy, permanent pacemaker placement, extracorporeal membrane oxygenation, heart catheterization, heart surgery subsequent to repair of TOF, dialysis (not peritoneal), and/or abdominal surgery. Kaplan-Meier analyses were performed for LOS for the three groups up to 60 days after surgery. Bivariate comparisons were made among groups; odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the control group as the comparator.

Results: There were 6,924 subjects (22q11 = 493, T21 = 455, controls = 5,976); 2,879 (42%) were female, and the mean age at surgery was 131 days (interquartile range [IQR] 80-190 days). Median postoperative LOS was 11 days (IQR 7-24) for 22q11, 7 days (IQR 5-12) for T21, and 6 days (IQR 5-10) for controls (p < 0.001 for all comparisons). Log-rank comparisons among groups also showed significant differences in Kaplan-Meier curves for LOS (Figure 1). Postoperative interventions were more common in 22q11 than either T21 or controls (p < 0.001 for all comparisons; Figure 2). In bivariate comparisons, 22q11 was associated with longer LOS compared to T21 (OR 2.37 [2.16, 2.60] vs. 1.25 [1.12, 1.39], p < 0.001). Occurrence of at least one postoperative intervention was also more common in 22q11 compared to T21 (OR 3.42 [CI 2.56, 4.57] vs. 1.38 [CI 0.91, 2.11]; p < 0.001).

Conclusion: Longer LOS and postoperative intervention after repair of TOF are more common in 22q11 compared to T21 and controls. The observed differences in postoperative morbidity support distinguishing between these syndromes when developing surgical quality metrics for repair of TOF.