Pathogen Detection by Metatranscriptomic Next Generation Sequencing in the Trophoblast Collected in Women Carrying a Fetus With Increasing Nuchal Translucency in the First Trimester of Pregnancy

Nuchal translucency > 3.5 mm in the first trimester of pregnancy is due to fluid accumulation in the subcutaneous tissue in the nuchal area. This is seen in around 1% of all pregnancies. Increased nuchal translucency is explained by a chromosomic abnormality (mainly Down syndrome) in 30 to 40% of cases. Therefore, the state of the art is to perform an array CGH on chorionic villi sampling. Cases of nuchal translucency that are not explained by a chromosomic abnormality may be associated: with fetal defect (heart, congenital diaphragmatic hernia) in 10% of cases, with genetic disease in 4% of cases or with miscarriage or fetal death of unknown etiology in 18% of cases.

The etiology of increased nuchal translucency remains unknown in more than 50% of the cases. It could be linked to inflammation or reflect an infection but this latter association has been rarely studied. This association was suggested in a study reporting serology of CMV, toxoplasmosis or B19 parvovirus primary infections in pregnant women carrying a fetus with increased nuchal translucency. In those rare cases, the microorganism was not searched directly in the trophoblast tissue. In the investigators' center, the investigators describe in a context of maternal primary infection, one case of increased nuchal translucency with a positive CMV PCR in the trophoblast tissue collected at 12 weeks. Other pathogens yet not identified might be associated with increased nuchal translucency.

Metatranscriptomic next generation sequencing (mNGS) allows to search for any pathogens without a priori. It is therefore a powerful technic to study this potential association between increased nuchal translucency and infection.