Is the first‐trimester combined screening result associated with the phenotype of Down syndrome? A population‐based cohort study

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.