Who is organizing first trimester screening?
A gynaecologist/obstetrician or other antenatal care provider (e.g., midwife, family doctor) will issue a referral letter for a free beta-HGT and PAPP-A at the same time as the referral for the first trimester sonography. After the first trimester fetal ultrasound and measurement of the thickness of the nuchal translucency, an ultrasound specialist will fill in or include additional information (if the antenatal care provider already issued) in the appropriate first trimester record regarding biochemical screening. The pregnant woman receives her blood serum marker tests no later than within 2 days after the ultrasonography.
How is genetic screening performed?
Genetic screening is performed in 3 steps:
All pregnant women irrespective of age have to perform the first trimester (within weeks 11 – 13 +6 days of pregnancy) fetal ultrasound and combined biochemical screening.
The hereditary anomalies risks evaluation is based on:
- the mother's age
- thickness of the nuchal fold
- measurements of the free βHGT and PAPP-A serum level
Patients with a risk of 1 in 50 or greater of a herediatry anomaly are included into the higher risk group and are sent to the prenatal diagnosis department/clinic. In the prenatal diagnosis department/clinic a gynaecologist with proficiency in prenatal diagnosis provides information regarding the need for diagnosis of the fetal karyotype.
Pregnant women of intermediate risk (with the measurement of risk 1:51 – 1:1000) are sent to the prenatal diagnosis department/clinic where patients consult with a gynaecologist with proficiency in the prenatal diagnosis; repeated ultrasound examination is performed and additionally first trimester ultrasound markers are evaluated during – 11th – 13th (+6 days) pregnancy week. At the same time, evaluation of the combined risk is performed in the case of negative ultrasound markers. Risk is evaluated for the following purpose: in the FMF accredited programme.
If the adjusted risk is ≥ 1 : 250, then the result is read as positive and the pregnant woman is recommended to undergo fetal karyotype diagnosis (chromosomal set) using invasive techniques.
If the adjusted risk is < 1 : 251, then the result is read as negative or low risk of fetal anomalies. In this case pregnant woman continues basic prenatal care at the gynaecologist – obstetrician (midwife, family doctor) .
In some cases pregnant women, in spite of receiving negative genetic screening results and normal fetal karyotype, are offered a fetal echocardiography.
If it is not possible to perform Step 2 risk evaluations during the first trimester, during the second trimester it is recommended to perform biochemical screening, having established three markers (triple test) – AFP, free HGT and uE 3 (estriol) during the 15th – 19th week of pregnancy and diagnosis of fetal ultrasound markers to take a decision regarding the necessity of invasive diagnosis for finding of chromosomal pathologies.
Gynaecologist consultations with proeficiency in prenatal diagnosis is recommended for women with an unknown origin of PAPP-A level in mother's serum during the first trimester or unknown origin raised level of HGT and AFP or low level of free estriol in mother's serum during the second trimester.
Detailed second trimester ultrasound (18th – 21st +6 days) for fetal anatomy and evaluation of development should be offered to all pregnant women.
If a woman's gestation period is more than 21 weeks (+6 days) and it is not possible to perform the triple test, US markers should be read together with the age.
If during the second trimester ultrasound an isolated inclusion in the cardiac structure was established („golf ball") although risk for Down syndrom after the first trimester screening results is lower than 1:1000 no further examination or repeated US is necessary. If after the first trimester screening results the risk for Down syndrom is higher than 1:1000, the patient is offered to amniocentesis testing. This boundary mark is chosen based on the fact such an inclusion in the cardiac structure during second trimester ultrasound doubles the risk for Down Syndrome.
If during the second trimester ultrasound a plexus chorioideus cyst is found, then there will be no referral for amniocentesis, only if this finding isn't connected with
The higher risk for Down syndrome or Edward's syndrome after screening results
Other pathology (-ies) during US examination
Maternal age – 35 years or more
If during the second trimester ultrasound more than one marker was established, or echogenic bowel , or enlarged nuchal fold size, or other structural or development anomalies, then the woman will be referred to a gynecologist with expertise in prenatal diagnosis.
Which methods are used in prenatal genetic diagnosis?
For prenatal diagnosis following methods are used:
- Ultrasound scans
- Detection of different biochemical markers in mother's blood and amniotic fluid
- Also invasive diagnostic techniques such as chorionic villus sampling and amniocentesis.
Are prenatal diagnosis techniques harmful?
Some of the prenatal diagnosis techniques are harmless (ultrasonography, detection of serum markers) but invasive techniques are associated with an insignificant risk for fetal development and pregnancy process.
Do all pregnant women have to do prenatal genetic diagnosis tests?
All pregnant women must undergo prenatal diagnostics.
Invasive (for example amniocentesis) genetic screening could be performed in case when mother's specific blood plasma biochemical and/or ultrasonography indicators are changed, because it is possible to confirm or exclude fetal chromosomal pathology only after analysis of fetal genetic material, which is obtained with a help of invasive diagnosis procedure (chorion or amniocentesis).
In which cases is necessary to consult with a genetic specialist?
Consultation regarding genetics and prenatal diagnosis testing is recommended in cases, when one of parents has chromosomal anomalies or hereditary disease and/or if there were structural or chromosomal anomalies established in fetus after performed prenatal testing.
What is a nuchal fold?
Soft tissue thickness within the nape of the fetal neck (NT – nuchal translucency)
Nuchal fold (NT – nuchal translucency) is a collection of fluid under the skin in the region of neck of the fetus - at the lower part of the skull and in the neck region, which is possible to determine with a help of the ultrasound technique.
Treatment options when fetus has enlarged nuchal fold?
In the case of an enlarged nuchal fold, between 11th and 14th week of gestation, it is recommended to perform a detailed ultrasound examination during the 18th – 20th weeks of pregnancy with a necessary assessment of the heart and large blood vessel structure. Fetal echocardiography is recommended as well.
Who can perform the measurement of a nuchal fold of the fetus?
During 1st trimester screening, assessment of the NT measurement must only be performed only by the specially trained and certified ultrasonography specialists in order to provide maximum quality of care.
What is the meaning of – biochemical markers? What is the use of BM?
During the 1st trimester, two biochemical markers appear in the mother's serum at the same time as NT (nuchal fold) is being examined. These are PAPP-A (pregnancy associated plasma protein A) and free β-hCG (human chorionic gonadotropin). If the fetus has genetic or congenital diseases these indicators will change.
If it is impossible to perform 1st trimester screening and/or obtain NT measurements, or it is impossible to perform 2nd step risk assessment during the I trimester, then 2nd trimester biochemical screening is advised – triple marker test. Having included one blood test during the time period from the 15th until 20th +6 week (best time is from the 15the +2 – 17th week).
What is amniocentesis?
This is a technique in prenatal diagnosis which gives an opportunity to obtain the fetal cells (amniocytes) out of the amniotic fluid. After performing analysis, the fetal material is multiplied for its testing for chromosome anomalies.
The collection of amniotic fluid is performed with the help of ultrasound control. A needle is injected through the external wall of the abdomen (through the skin, subcutaneous tissue, and the wall of the uterus) and collects 10 – 15 ml of amniotic fluid.
To be able to see the location of placental attachment and location of the fetus, the puncture is performed in the upper part of uterus using ultrasound control. Usually amniocentesis is recommended from the 15th until 20th (+6days) pregnancy week. Possible side effects from amniocentesis are: fetal trauma, preterm birth, infant respiratory distress, posture pathology in childhood, mother's isoimmunization (antibodies appearing in mother's blood), amniotic fluid embolism, and infection.
However, it is believed that the pregnancy interruption risk related to the procedure does not exceed 0.6 – 0.86%.
What is a Chorion Villus Sampling?
A chorion villus sampling is an invasive prenatal diagnosis technique for detection of chromosome or genetic pathologies of the fetus. Usually chorion villus sampling is performed during the 11th until the 12th (+6 days) pregnancy week. There are risks related to the procedure which include getting an infection, leaking of amniotic fluid, the developing of low level of amniotic fluid, and pregnancy interruption in 0.5 – 1% of cases.