Fields of treatment / Gynecology / Medical genetics

Prenatal genetic testing (amniocentesis, chorionic villus sampling) can tell for sure if the baby is likely to have a genetic condition early in the pregnancy.

Prenatal genetic testing also includes examinations and consultations to assess associated external fetal risks (side effect of certain medications, external factors, working conditions) or internal fetal risk (occurrence of certain disease in the female)

Finally, our medical genetics department provides genetic testing as we treat couples for infertility or repeated miscarriages.

• Genetic disease, birth defect in your family
• Your previous child was born with a birth defect
• You are infertile or have had miscarriages
• You are a pregnant woman aged over 35 or a male over 45 trying to conceive
• You are pregnant and have a positive genetic screening test result
• You are pregnant woman and have had infections, certain medications or you are treated with radiotherapy
• Consanguineous marriage

by Kypros Nicolaides, Rosalinde Snijders

In 1866 Langdon Down noted that common characteristics of patients with trisomy 21 are skin deficient in elasticity, giving the appearance of being too large for the body, and flat face with a small nose. In the 1990s, it was realized that the excess skin of individuals with Down’s syndrome can be visualized by ultrasonography as increased nuchal translucency in the third month of intrauterine life. Fetal nuchal translucency thickness at the 11–13+6 weeks scan has been combined with maternal age to provide an effective method of screening for trisomy 21; for an invasive testing rate of 5%, about 75% of trisomic pregnancies can be identified. When maternal serum free ß-human chorionic gonadotropin and pregnancy-associated plasma protein-A at 11–13+6 weeks are also taken into account, the detection rate of chromosomal defects is about 85–90%.

In 2001, it was found that in 60–70% of fetuses with trisomy 21 the nasal bone is not visible at the 11–13+6 weeks scan and examination of the nasal bone can increase the detection rate of screening by the first trimester scan and serum biochemistry to more than 95%. In addition to its role in the assessment of risk for trisomy 21, increased nuchal translucency thickness can also identify a high proportion of other chromosomal defects and is associated with major abnormalities of the heart and great arteries, and a wide range of genetic syndromes.

Other benefits of the 11–13+6 weeks scan include confirmation that the fetus is alive, accurate dating of the pregnancy, early diagnosis of major fetal abnormalities, and the detection of multiple pregnancies. The early scan also provides reliable identification of chorionicity, which is the main determinant of outcome in multiple pregnancies.

As with the introduction of any new technology into routine clinical practice, it is essential that those undertaking the 11–13+6 weeks scan are adequately trained and their results are subjected to rigorous audit. The Fetal Medicine Foundation has introduced a process of training and certification to help to establish high standards of scanning on an international basis. The Certificate of Competence in the 11–13+6 weeks scan is awarded to those sonographers that can perform the scan to a high standard and can demonstrate a good knowledge of the diagnostic features and management of the conditions identified by this scan.

Screening is done based on a certificate that was obtained at the Fetal Medicine Foundation (FMF) London with Professor. Kypros Nicolaides after completing the theoretical and practical part of the course. The quality of the screening is guaranteed by the certificate. Also, a regular audit is held annually to confirm its validity.

The combined screening consists of 2 parts, biochemical (determination of free ß HCG and PAPP-A) and ultrasound (CRL, NT, FHR and other markers). The results of the biochemical and ultrasound screening are then assessed by special software, for which I have been licensed upon certification. Based on this evaluation, we can determine the individual risk of aneuploidy (e.g. Down syndrome).

Females with a low risk (less than 1:1000) are allowed to proceed and I recommend a genetic ultrasound, which I do at 20-22 weeks of gestation. If a female is at high risk of trisomy (risk greater than 1:100), they are informed and recommended transabdominal chorionic villus sampling (CVS). If they agree, I perform the sampling immediately. The material obtained is processed in an accredited genetic laboratory, GENNET. The results are available next day The patient is informed by phone about the result of the genetic test and when chromosomal defect is confirmed, the patient might decide to have an abortion. If the patient agrees or requests termination of their pregnancy, we perform this procedure in the usual way. At this point, we would like to stress the speed, gentleness and much less psychological burden on the patient. There is another option, however, which involves second trimester screening at 16 weeks of gestation. This requires waiting and termination of pregnancy that far along pregnancy carries some risks.

In women with intermediate risk (i.e., risk range from 1:999 to 1:100), additional ultrasound markers of trisomy are obtained. As standard, nasal bone identification is performed (NB, absence of a bone is assessed as a positive finding), tricuspid valve flow (regurgitation at either tip of the valve is assessed as positive), and ductus venosus Arantii flow (evidence of regurgitation is positive). If the result is positive for at least one of these markers, further management is the same as for high-risk women. If results turn negative, the same procedure is followed as in low-risk women Next examination (ultrasound) is performed only at 20th week of gestation.