Clinicians should carefully consider using noninvasive prenatal testing (NIPT) for the screening of chromosomal abnormalities in twin pregnancies because the combined positive predictive value (PPV) is limited and the screening efficiency is not stable, according to a prospective study.
The study in the journal Molecular Cytogenetics found that the combined PPV was only 15.4% among the 13 twin pregnancies with positive NIPT results.
“The superior performance of NIPT in singleton pregnancies is recognized as an almost perfect screening method, which makes the medical community and the public hopeful that the test technology can be equally applicable for pregnant women with twin pregnancies,” wrote the authors.
Recent studies of NIPT in twin pregnancies have mostly assessed trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13), according to the authors, but the use of NIPT for sex chromosome diseases, microdeletions and microduplications has not been systematically evaluated.
“This is the first prospective study in which NIPT simultaneously detected autosomes and sex chromosome aneuploidies, microdeletions and microduplications as well in twin pregnancies,” they wrote.
Over a 4-year period, from March 2016 to September 2020, a total of 1,048 women with twin pregnancies were voluntarily prospectively tested by NIPT to screen for chromosomal abnormalities by sequencing cell-free foetal DNA (cffDNA) in maternal plasma at the Maternity and Child Health Hospital of Anhui Province in China.
Overall, 87.5% of the pregnant women were under the age of 35 and most women had no previous risk factors, thus representing the general obstetric population.
Positive NIPT results were confirmed by karyotyping, while negative outcomes were followed up 42 days after delivery.
Among the 13 women with positive NIPT results, there were 2 cases of T21; 1 case of T18; 7 cases of sex chromosome aneuploidy (SCA); 1 case of microdeletion; and 2 cases of microduplication.
Of the 13 cases, only 2 were true-positive cases confirmed by foetal karyotype analysis: 1 case each of T21 and microdeletion.
The remaining 11 high-risk pregnant women were confirmed as false positive by foetal karyotyping. There were no false-negative cases during follow-up.
The combined PPV of NIPT for screening T21 and T18 was 33.3%, while the PPV for T21 was 50%.
The authors noted that NIPT evaluates free placental DNA, not foetal DNA, and that placental mosaicism compromises its performance in screening for foetal chromosomal abnormalities; hence, it cannot be absolutely confirmed that the cause of false positives in the study is restricted to confined placental mosaicism.
Studies have shown that NIPT screening cannot completely avoid false-positive results, according to the authors, due to confounders such as confined placental mosaicism, maternal mosaicism, chromosome copy number variation, and maternal tumors. “Therefore, when NIPT results are inconsistent with karyotype results, clinicians should be patient in the process of interpretation,” they said, adding that clinicians should reasonably guide high-risk pregnant women to verify the result by amniotic fluid puncture with the Z value, cffDNA concentration, and B ultrasound.
“In summary, NIPT based on high-throughput sequencing is a screening technique rather than a diagnostic technique, and its performance in twin pregnancies is weaker than that in singleton pregnancies,” wrote the authors.