Case Report from Turkey: Fetal Aneuploidy Detection by Cell-Free fetal DNA Sequencing for Multiple Pregnancies and Quality Issues with Vanishing Twin
In the case of multiple pregnancies, conventional non-invasive examination methods for the determination of fetal trisomies have limitations while invasive methods bear higher risk for procedure related fetal losses when compared to singleton pregnancies. Therefore, non-invasive prenatal testing (NIPT) by random massively parallel sequencing (rMPS) from maternal blood for multiple pregnancies can be a reliable option in prenatal care. However, NIPT might have quality issues in case of multiple pregnancies. For example, vanishing twins might cause, as described in the case report.
The results show that the first NIPT result positive for fetal trisomy 21 was caused by the trisomic cffDNA of the vanishing twin. The difference between the level of cffDNA measured by QuantYfeX® and the Y-chromosomal representation in both blood samples of the first blood draw is due to the presence of the deceased female fetus and the living male fetus, both releasing cffDNA into the mother’s blood circulation.
The case report demonstrates that vanishing twins are a limiting factor for NIPT, as undisclosed vanishing twins can contribute a sufficient proportion of cffDNA to the total amount of cffDNA to cause a positive PraenaTest® result being not representative for the continuing singleton pregnancy.Therefore, such pregnancies need to be monitored thoroughly during clinical care in order to be able to interpret NIPT results correctly. So far there have not been any studies which describe in any way whether the size of a vanishing twin or the size of its amniotic cavity correlate with the level of cffDNA in the maternal plasma.It also needs to be investigated whether a vanishing twin might cause a cffDNA flooding into the maternal circulation as a result of dying cells which are increasingly releasing fetal DNA. In the future, for a better understanding and interpretation of NIPT results of such cases a more detailed documentation of the progress of vanishing twins in combination with NIPT results is needed.
We recommend responsible physicians to discuss each individual case with us. We would suggest not to perform the PrenaTest® as long as the vanishing twin and/or the amniotic cavity can still be detected during ultrasound examination, since a positive test result cannot clarify which of the twins is affected with the detected fetal trisomy. On the other side, a negative test result should confirm that the living fetus is not affected, as long as the measured level of cffDNA is at least 8% which is the minimum amount required for a successful PrenaTest® analysis of twin pregnancies.However, since many vanishing twins remain unrecognized,discordant NIPT results can never be ruled out in general. Therefore, the existence of such cases underpins the recommendation of medical associations that NIPT should be offered only after, or in conjunction with a qualified ultrasound examination.
Reference: Groemminger, S.et al. J. Clin. Med. 2014, 3, 679-692; doi:10.3390/jcm3030679