First-trimester screening for trisomies by cfDNA testing of maternal blood in singleton and twin pregnancies: factors affecting test failure

Abstract

Objective: To examine factors affecting the rate of failure to obtain a result from cell-free DNA (cfDNA) testing of maternal blood for fetal trisomies 21, 18 and 13 in singleton and twin pregnancies in the first trimester. Methods: This was a prospective study of 23 495 singleton and 928 twin pregnancies undergoing screening for fetal trisomy by targeted cfDNA testing at 10 + 0 to 14 + 1 weeks' gestation. Multivariate logistic regression analysis was used to determine significant predictors of failure to obtain a result after first sampling. Results: There was no result from cfDNA testing after first sampling in 3.4% (798/23 495) of singletons, 11.3% (91/806) of dichorionic twins and 4.9% (6/122) of monochorionic twins. Multivariate logistic regression analysis demonstrated that the risk of test failure, first, increased with increasing maternal age (odds ratio (OR), 1.02; 95% CI, 1.01–1.04) and weight (OR, 1.05; 95% CI, 1.04–1.05), decreasing gestational age (OR, 0.85; 95% CI, 0.79–0.91), serum pregnancy-associated plasma protein-A (PAPP-A) multiples of the median (MoM) (OR, 0.56; 95% CI, 0.49–0.65) and free β-human chorionic gonadotropin (β-hCG) MoM (OR, 0.67; 95% CI, 0.60–0.74), second, was higher in women of black (OR, 1.72; 95% CI, 1.33–2.20) and South Asian (OR, 1.99; 95% CI, 1.56–2.52) than those of white racial origin, in dichorionic twin than in singleton pregnancy (OR, 1.75; 95% CI, 1.34–2.26) and in pregnancies conceived by in-vitro fertilization than in those conceived naturally (OR, 3.82; 95% CI, 3.19–4.55) and, third, was lower in parous than in nulliparous women (OR, 0.63; 95% CI, 0.55–0.74). Conclusions: Maternal age, weight, racial origin and parity, gestational age, dichorionicity, method of conception and serum levels of free β-hCG and PAPP-A are independent predictors of cfDNA test failure. The risk of test failure is higher in dichorionic twin than in singleton pregnancies, mainly because a higher proportion of twins are conceived by in-vitro fertilization and more of the women are nulliparous. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.