Soft Markers of Aneuploidy in the Second Trimester: Significance in the Era of NIPT
Context: NIPT and Prenatal Screening
Non-invasive prenatal testing (NIPT, cell-free DNA / cfDNA) has substantially altered the structure of prenatal screening for aneuploidy. Following NIPT implementation, changes in screening coverage for chromosomal pathology have been documented in population studies (van der Meij KRM et al., Acta Obstet Gynecol Scand). The accuracy of cfDNA testing depends on several factors, including body mass index, which affects fetal fraction and the probability of test failure (Rolnik DL et al., Obstet Gynecol 2018; Galeva S et al., Ultrasound Obstet Gynecol 2019).
Soft Markers in the Structure of Prenatal Diagnosis
In one of the presented studies (Ultrasound in Obstetrics & Gynecology, Vol. 63, №4), it is directly stated that prenatal diagnoses did not include soft markers for aneuploidy ("Prenatal diagnoses did not include soft markers for aneuploidy"). This reflects a trend toward reassessing the independent clinical significance of isolated soft markers in the context of NIPT availability.
Specific ultrasound soft markers of the second trimester, their threshold values, and likelihood ratios are not provided in the available fragments. Additional sources are required to establish a threshold value table [clarification needed].
Factors Affecting cfDNA Test Accuracy
| Factor | Impact on cfDNA Test | Source (from fragments) |
|---|---|---|
| Body mass index | Affects fetal fraction increase with gestation and probability of test failure | Rolnik DL et al., 2018 |
| Uterine fibroid | Affects the accuracy of cfDNA screening | Scott F et al., 2022 |
| Multiple pregnancy / vanishing twin | Quality considerations and detection specifics in multiple pregnancies | Gromminger S et al., 2014; Kantor V et al., 2022 |
Early Structural Findings as Priority
According to the fragments, detection of structural anomalies and the role of aneuploidy markers are considered as early as the 11–14-week ultrasound scan (Grande M et al., Ultrasound Obstet Gynecol 2012; Bilardo C, Chaoui R, Hyett J et al., ISUOG Practice Guidelines). Early findings—cystic hygroma, fetal edema—are discussed in the context of referral pathways before/after NIPT (Scholl J, Chasen ST, 2016; Rambkrishna J et al., 2021).
Practical conclusion: in the era of NIPT, the emphasis shifts toward detection of structural anomalies and early assessment; isolated soft markers in a number of modern protocols are not regarded as an independent diagnosis. Specific thresholds and algorithms require clarification according to relevant clinical guidelines [clarification needed].
Frequently asked questions
Are isolated soft markers included in the prenatal diagnosis in contemporary studies?
In one of the presented studies (Ultrasound in Obstetrics & Gynecology, Vol. 63, №4), it is directly stated that prenatal diagnoses did not include soft markers for aneuploidy.
What factors reduce the accuracy of NIPT?
According to the fragments: elevated BMI (affecting fetal fraction and test failure), presence of uterine fibroids, and multiple pregnancy and vanishing twin phenomenon.
Are specific threshold values for soft markers provided in the source?
No. Specific ultrasound markers, their thresholds, and likelihood ratios are not present in the available fragments [clarification needed].
At what gestational age does assessment of aneuploidy markers begin?
According to the fragments, detection of structural anomalies and the role of aneuploidy markers are considered as early as the 11–14-week ultrasound scan (ISUOG Practice Guidelines; Grande M et al., 2012).