The care of pregnant women centres on combined first trimester screening (“first-trimester screening”).

This aims to detect common types of trisomy, such as trisomy 21, responsible for Down syndrome, as well as trisomies 18 and 13. The three components making it possible to determine the risk of trisomy include ultrasound measurement of nuchal translucency (NT), a blood test measuring two biomarkers (PAPP-A and B-hCG), as well as the mother's age.

The results of first-trimester screening allow the categorisation of various classes of risk. If the risk is very low (<1:1000), no particular monitoring is planned. If the risk is intermediate (>1:1000, but <1:100 or <1:50) non-invasive screening (NIPT) is indicated, the cost of which is covered by health insurance. If the risk is high (variable definition, >1:100 or >1:50), invasive prenatal testing (IPD) is recommended, involving chorionic villus sampling from the eleventh week of pregnancy).

When a specific chromosomal abnormality is suspected, or non-invasive screening indicates an abnormality, karyotype analysis with amniotic fluid is necessary in order to confirm or rule out the diagnosis. If the karyotype proves to be normal, additional tests will be planned.

The precise nature of the additional tests depends on the context, mainly the size of the NT and the presence of malformations or foetal abnormalities (e.g. retarded growth or hydramnios).

In the case of isolated, significantly increased NT thickness (the definition of this varies, either ≥3mm or ≥3.5mm; Acta Obstet Gynecol Scand 2020; 99:765-774), then a combination of FISH or QF-PCR may be prescribed as first line treatment to detect common autosomal trisomies and sex chromosome abnormalities (otherwise known as gonosomal abnormalities).

If this is normal, a test aimed at detecting structural chromosome abnormalities that are not identified by karyotype resolution may be suggested (comparative genomic hybridisation, or CGH). One or more malformations (particularly malformations of the heart and central nervous system), retarded growth or hydramnios are independent indications for CGH, if the first phase has not revealed any anomalies (Obstet Gynecol 2018; 132:1368-1375).

If the CGH has not identified an anomaly that is either pathogenic or probably pathogenic, clinical exome sequencing may be proposed to search for mutations responsible for monogenic diseases and syndromes (Lancet 2019:393: 747-57). Various different options are available, depending on the disease, and particularly gene panels (e.g. to search for the causes of isolated or syndromic heart defects), or alternatively exhaustive testing (e.g. the 5,430 disease-associated genes known as CDGs (closest disease-causing genes) (Front. Immunol .2018; 9:1340).

Indications are as follows: NT ≥3.5 mm, hydramnios, heart, brain or kidney malformation, growth anomaly, cleft lips and palates, limb abnormalities (polysyndactyly, ectrodactyly), arthrogryposis, and the combination of several ultrasound signs.

Genesupport - Risk during pregnancy