Comment on “Long-term Survival Among Children With Trisomy 13 and Trisomy 18 by Cytogenetic Status”

Trisomy 13 (T13, Patau syndrome) and trisomy 18 (T18, Edwards syndrome) are the second and third most common autosomal trisomies after trisomy 21. Affected children often have multiple congenital anomalies, with substantial morbidity and low survival beyond the first year of life. Trisomies may occur as full trisomies, in which all cells contain 3 copies of a chromosome; mosaic trisomies, in which only a subset of cells are trisomic; or partial trisomies, in which each cell has 3 copies of part of a chromosome and 2 copies of the rest. While case series suggest potential differences in outcomes across these variants, large-scale population-based data on long-term prognosis by cytogenetic status are limited. This study compares 10-year survival rates between full, mosaic, and partial trisomies among children with T13 and T18 using a large population-based cohort. This retrospective cohort study used data from the Texas Birth Defects Registry (TBDR), which collects information on all Texas deliveries in which infants are diagnosed with chromosomal or structural abnormalities prenatally or within 1 year of life. Infants were included if they were delivered between 1999 and 2008, had a diagnosis of T13 or T18, and had available cytogenetic information. Due to the low prevalence of mosaic and partial trisomies, these groups were combined into a single nonfull trisomy category for analysis. Cases were excluded if the pregnancy ended in termination, spontaneous fetal death, or if additional trisomies were present. The primary outcome was survival to 10 years of age by cytogenic status, with separate analyses for T13 and T18. Covariate analyses included univariate adjustment for potential confounders such as maternal age and ethnicity, and secondary analyses assessed for the presence of additional unidentified confounding. A total of 798 infants were included, including 295 with T13 and 503 with T18. Among infants with T13, 17.6% had nonfull trisomies, while 6.4% of those with T18. The survival rate to 10 years of age was 8.5% (95% CI, 5.5%-12.3%) for T13 and 8.6% (95% CI, 6.3%-11.3%) for T18. Survival was substantially higher among infants with nonfull trisomies, reaching 25% for T13 and 43.8% for T18. Full trisomy was associated with significantly higher 10-year mortality compared with nonfull trisomy, with hazard ratios of 2.00 (95% CI, 1.42-2.82) for T13 and 3.34 (95% CI, 2.08-5.38) for T18. Population attributable fraction analysis estimated that 41.7% of 10-year survival among infants with T13 and 27.9% among infants with T18 was attributable to nonfull trisomy status. Secondary analyses showed no meaningful change in effect estimates after adjustment for measured confounders. Sensitivity analyses indicated that an unknown confounder would need to have a magnitude of association with cytogenetic status of 2.61 for T13 infants and 3.98 for T18 infants in order to significantly alter these findings. Overall, survival to 10 years of age was about twice as high among infants with nonfull T13 and 3 times as high among those with nonfull T18 compared with full trisomy. In this population, quality of life considerations have often led clinicians and families to favor comfort-focused care over invasive corrective surgeries due to perceived low survival rates. The results suggest that cytogenetic status should be considered in these clinical decisions. Strengths of this study include a large, long-term, population-based dataset, while limitations include a low total number of T13 and T18 cases due to rarity, limited related health data, and potentially incomplete death certificate records. (Summarized from Ludorf KL, Benjamin RH, Shumate CJ, et al. Long-term survival among children with trisomy 13 and trisomy 18 by cytogenetic status. JAMA Netw Open. 2025;8(9):e2529885. doi: https://doi.org/10.1001/jamanetworkopen.2025.29885.)