Is the first‐trimester combined screening result associated with the phenotype of Down syndrome? A population‐based cohort study. (13th December 2022)

• Record Type: Journal Article
• Authors: Steffensen, Ellen Hollands; Pedersen, Lars Henning; Lou, Stina; Vogel, Ida
• Is Part Of: Prenatal diagnosis. Volume 43:Number 1(2023)
• Page Start: 51
• Page End: 61
• Publication Date: 2022-12-13
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.6284
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Objective: To investigate if the Down syndrome phenotype differs according to the result of first‐trimester combined screening (FTS). Method: We included all Down syndrome cases diagnosed by karyotype in pregnancy or after birth in Denmark during 2005–2018. We compared screen positive (odds ≥1:300) and screen negative (odds <1:300) cases as well as screen result subgroups with respect to anthropometrics, congenital malformations, childhood diseases, and hospitalization. Results: Absolute measures of fetal and birth anthropometrics were comparable between groups. A prenatal malformation diagnosis was more prevalent among screen positive than screen negative cases. Analyses suggested that this could reflect a detection bias. Cases with a screen result of 1:2–1:10 had a higher probability of being diagnosed with a malformation prenatally and with severe congenital heart disease (CHD) postnatally compared with a result of 1:11–1:300. Screen positive cases more often had non‐severe CHD but less often a non‐heart malformation compared with screen negative cases, while proportions of severe CHD were similar in these groups. Data on hospitalizations showed inconsistent results. Conclusion: The 1:300 screening threshold had limited or no value in predicting Down syndrome phenotype severity. In contrast, cases with a screen result between 1:2 and 1:10 may represent a more severe phenotype. Key points: What's already known about this topic? The severity of the Down syndrome phenotype is variable and unpredictable. The first‐trimester combined screening (FTS) is based on measures, such as nuchal translucency, known to be associated with adverse outcomes, suggesting predictive potential. What does this study add? The severity of the Down syndrome phenotype did not consistently differ between screen positive (odds at FTS ≥1:300) and screen negative (odds at FTS <1:300) cases. Screen positive Down syndrome cases with odds 1:2–1:10 may, however, be at risk of a severe phenotype. In screen negative Down syndrome cases, the sensitivity of a prenatal diagnosis of congenital malformations may be lower than that among screen positive Down syndrome cases.