Fellow Physician Nationwide Children's Hospital Columbus, Ohio, United States
Background: Down Syndrome (T21), Edwards Syndrome (T18), and Patau Syndrome (T13) are the most common autosomal aneuploidies at birth. As prenatal screening via cell free fetal DNA becomes more common, the index of suspicion for postnatal diagnosis becomes increasingly important for cases not identified before birth. It is well known that clinicians are less adept at recognizing dysmorphology in children from non-European ancestry, in part because almost all educational material focuses on pictures of European ancestry children. We hypothesized that because educational materials also include few photos of premature infants with these conditions, prematurity may be associated with delayed postnatal diagnosis. Objective: To determine if preterm neonates with T13/18 or T21 admitted to the NICU are diagnosed later in life than their term counterparts. Design/Methods: Neonates with a postnatal diagnosis of T13, 18, or 21 admitted to any Nationwide Children’s Hospital NICU from 2010-2021 were evaluated. We excluded neonates with a confirmed diagnosis or a positive prenatal screen noted on admission, as well as those diagnosed after one year of age. Diagnoses of T13/18 were analyzed together as we hypothesized that the marked dysmorphology associated with these conditions would render them less likely to be impacted by prematurity than T21. The primary exposure was gestational age (GA) at birth: < 34 weeks (preterm), 34-36 weeks (late-preterm) and ≥ 37 weeks (term/post-term). Time to diagnosis was compared between GA groups for T13/18 and T21 separately using the Jonckheere-Terpstra rank-based nonparametric test for ordered alternatives. Results: 177 neonates with T21 and 36 with T13/18 were included (see figure 1, CONSORT diagram). Race distribution was similar between groups (table 1). Among neonates with T21, the median age [days (interquartile range)] at karyotypic diagnosis for all GAs was 8 (5-19), and for term/post-term, late preterm, and preterm neonates was 7 (5-13), 11 (6-25) and 12 (6-30), respectively. The trend of increasing age at diagnosis with increasing degrees of prematurity was significant (p <.001). Among neonates with T13/18, the median age at karyotypic diagnosis for all GAs was 6 (4-7), and for term/post-term, late-preterm, and preterm neonates was 6 (4-6), 6 (3-12), and 5 (4-7), respectively, with no significant trend by GA category.
Conclusion(s): Increasing prematurity is associated with increasing age at diagnosis of T21 but not T13/18 in a large network of Level III and IV NICUs. Longer time to diagnosis could delay appropriate medical care, genetic counseling, and psychosocial support.