Non‐invasive prenatal testing (NIPT) in twin pregnancies affected by early single fetal demise: A systematic review of NIPT and vanishing twins

The screening performance of non‐invasive prenatal testing (NIPT) in vanishing twin (VT) pregnancies is relatively unknown. To close this knowledge gap, we conducted a systematic review of the available literature. Studies describing the test performance of NIPT for trisomy 21, 18, 13, sex chromosomes and additional findings in pregnancies with a VT were retrieved from a literature search with a publication date until October 4, 2022. The methodological quality of the studies was assessed with the quality assessment tool for diagnostic accuracy studies‐2 (QUADAS‐2). The screen positive rate of the pooled data and the pooled positive predictive value (PPV) were calculated using a random effects model. Seven studies, with cohort sizes ranging from 5 to 767, were included. The screen positive rate of the pooled data for trisomy 21 was 35/1592 (2.2%), with a PPV of 20% (confirmation in 7/35 cases [95% CI 9.8%–36%]). For trisomy 18, the screen positive rate was 13/1592 (0.91%) and the pooled PPV 25% [95% CI 1.3%–90%]. The screen positive rate for trisomy 13 was 7/1592 (0.44%) and confirmed in 0/7 cases (pooled PPV 0% [95% CI 0%–100%]). The screen positive rate for additional findings was 23/767 (2.9%), of which none could be confirmed. No discordant negative results were reported. There is insufficient data to fully evaluate NIPT performance in pregnancies with a VT. However, existing studies suggest that NIPT can successfully detect common autosomal aneuploidies in pregnancies affected by a VT but with a higher false positive rate. Further studies are needed to determine the optimal timing of NIPT in VT pregnancies. Key points What is already known about this topic? Non‐invasive prenatal screening testing (NIPT) is being offered worldwide to detect chromosomal aberrations by analyzing cell‐free DNA. Aneuploidy is a major cause of first trimester loss/vanishing twins. Therefore, a vanishing twin (VT) can complicate the interpretation of NIPT. Guidelines and healthcare providers generally advise against the use of NIPT in VT pregnancies due to uncertain screening performance. What does this review add? This is the first systematic review on the test performance of NIPT, creating an overview and interpretation of the existing data. There was insufficient data to fully evaluate NIPT performance in pregnancies with VT. However, existing studies suggest that NIPT can successfully detect common autosomal aneuploidies in pregnancies affected by a VT but with a higher