What are the stages in a normal pregnancy?
- Positive pregnancy test – no longer confirmed at GP
- Book into antenatal care – see midwife
1. Nuchal scan – 10-14 weeks gestation. Different tests dependent upon NHS Trust e.g. nuchal translucency, combined test etc.
2. Mid-trimester anomaly scan
3. Ultrasound examination is the main method for prenatal diagnosis of fetal abnormalities. 4. All pregnant women should be offered routine ultrasound scans at 11-14 weeks and again at 20-22 weeks.
What are the aims of the 12 week scan?
- To date the pregnancy accurately.
- To diagnose multiple pregnancy.
- To diagnose major fetal abnormalities.
- To diagnose early miscarriage.
- To assess the risks of Down Syndrome and other chromosomal abnormalities.
- Taking into account the maternal age, blood hormone levels, nuchal translucency thickness, nasal bone, blood flow through the fetal heart and fetal abnormalities.
When is the Nuchal translucency test?
- 10-14 weeks
- Look at thickness of fluid at back of fetal neck
- NT is screening test and is not diagnostic
What can it indicate if the thickness at back of fetal neck is greater than 3mm?
1. Chromosome abnormalities (e.g. Downs, Edwards, Patau, Turners) NT + maternal age detects up to 75% of Down syndrome with 5% false positive rate 2. Birth defects: - Cardiac anomalies Pulmonary defects (diaphragmatic hernia) Renal defects Abdominal wall defects 3. Skeletal dysplasias (Check)
When is prenatal testing arranged?
- Following abnormal findings at nuchal scan or mid-trimester scan
- Following results of combined test which give an increased risk of Down Syndrome
- If previous pregnancy affected with a condition e.g. DS, CF
- If parent(s) carrier of chromosome rearrangement or genetic condition, e.g. t(13;14), DMD, HD.
- FH of genetic condition
What are the aims of prenatal testing?
1 .To inform and prepare parents for the birth of an affected baby
2. To allow in utero treatment
3. Manage the remainder of the pregnancy
4 .To be prepared for complications at or after birth
5. To allow termination of an affected fetus
What are the scanning prenatal tests?
Ultrasound/MRI
What are the non-invasive prenatal tests?
Maternal blood test
Cell-free fetal DNA
What are invasive pre-natal tests?
Chorionic villus sampling (CVS)
Amniocentesis
What are the different ultrasounds in pregnancy?
Early / dating scan
Nuchal translucency (NT) & nasal bone
High level / anomaly scan
When is there usually a metal MRI?
Usually around 20 weeks+
What does examination of metal profile increase sensitivity of screening for?
Downs syndrome
What is maternal serum screening? What does it find?
- Tests maternal serum markers in the blood to detect:
- increased risk of fetal trisomy 21, trisomy 18 and/or neural tube defects - 1st trimester maternal serum screening (with nuchal translucency measurement): 11-14 weeks [hCG, PAPP A]
- 2nd trimester maternal serum screening (triple screen): 16-20 weeks [AFP, uE3, hCG]
- Nuchal translucency measurement: 11-14 weeks
- Other variations combining 1st and 2nd trimester screening results available privately
What is cell free metal DNA>
- Non-invasive prenatal diagnosis (NIPD) works by analysing the DNA fragments present in the maternal plasma during pregnancy (cell-free DNA).
- Most of this DNA comes from the mother
- 10%-20% of it comes from the placenta, which is representative of the unborn baby (cell-free fetal DNA).
- Cell-free fetal DNA (cffDNA) is first detectable from about 4 -5 weeks’ gestation, but cannot accurately be detected on testing until around 9 weeks
What is NIPD? When is it free?
•Maternal blood test at around 9 weeks of pregnancy
- Achondroplasia - testing is free
- Thanatophoric dysplasia - testing is free
- Apert syndrome- testing is free
When is sexing offered and when is non invasive test required?
SEXING
•Currently offered when there is a X-linked condition in the family e.g. DMD.
•Test detects SRY gene on Y chromosome, enabling us to determine if male or female fetus
–If male-go on to prenatal test
–If female -no invasive test required
When is NIPD offered privately via NHS?
•Autosomal dominant single gene disorders inherited from the father or arisede novo
–NF1
•NIPD is also possible to alter management of pregnancies at risk of recessive conditions when the mother and father carry different altered genes.
–if the paternal alterationhas been inherited by the fetus invasive prenatal testing can be offered.
- Cystic fibrosis – haplotyping (RHDO) can test for both maternal and paternal mutation
cffDNA testing for Aneuploidy (NIPT)
•Offered privately (Harmony) or via research studies
•Harmony currently test for T13, T18, T21 and this identifies:
–99% of fetuses with trisomy 21
–97% of fetuses with trisomy 18
–92% of fetuses with trisomy 13.
•Is this accurate enough to make a decision?
What are the basic symbols?
- Translation of non-invasive prenatal diagnosis (NIPD) for Duchenne and Becker Muscular Dystrophy (DMD/BMD) into a clinical setting.
- Evaluating early non-invasive prenatal diagnosis (NIPD) based on cell-free fetal (cff) DNA and RNA in maternal plasma.
What are the limitations of NIPD and NIPT?
1 .Multiple pregnancies - It is not possible to tell which fetus the DNA is from when carrying twins/triplets etc.
- The relative proportion of cell-free fetal DNA is reduced in women with a high BMI as they have more of their own cell-free DNA.
- Although it is just a blood test, it has the same implications as an invasive test.
- Women may prepare themselves more for the implications of an invasive test result
- Women must consider the consequences of the results. Do they want this information?
- An invasive test may still be required to confirm an abnormal result.
What are the benefits of NIPD and NIPT?
- The number of invasive tests carried out is likely to reduce as a result
- There is no increased risk of miscarriage.
- Less expertise is required to perform a blood test than an invasive test.
- In many cases we can offer NIPD /NIPT earlier than traditional invasive testing, thereby getting a result much earlier.
When are invasive tests offered?
•Offered if there is a ‘known risk’ –Chorionic villus sampling (CVS) –Amniocentesis •Molecular, cytogenetic and biochemical tests •Ultrasound guidance •Outpatient basis
When is chorionic villus sampling (CVS) offered? What is the risk of miscarriage?
–11-14 weeks
–1-2% risk of miscarriage
–Transabdominal or transvaginal
–Takes sample of chorionic villi – part of developing placenta – same DNA as fetus
–Allows patient to have an earlier result than amnio - important for many patients re. TOP decision
What are the different methods of CVS? What does it entail?
–Transabdominal or transvaginal
–Takes sample of chorionic villi – part of developing placenta – same DNA as fetus
–Allows patient to have an earlier result than amnio - important for many patients re. TOP decision
When is amniocentesis carried out?
–From 16 weeks
–Takes sample of amniotic fluid which contains fetal cells
-
Integration of metabolism57
-
Cell Metabolism 163
-
ATP production15
-
Cell Metabolism 28
-
Red Cells18
-
White cells18
-
Plasma23
-
Cholesterol12
-
Epithelial Cells18
-
Inflammation36
-
Fluid compartments and solutes15
-
Extracellular matrix (ECM)34
-
Cell Signalling18
-
Cell replication25
-
Cell Injury and fate15
-
Haemostasis33
-
Hypersensitivity40
-
Blood Transfusion37
-
Microbial Infections12
-
Hospital Acquired Infection and Antibiotic Resistance33
-
Cancer26
-
Lymphocytes22
-
Modes of Inheritance28
-
Regulation of Lymphocytes33
-
Blood Cell Abnormalities31
-
Phenotypic Variability29
-
Emerging treatments49
-
Prenatal testing39
-
Cancer Genetics42
-
Immune Evasion by Lymphocytes53
-
Vaccines22
-
Genetic Disorders8
-
Chromosomal Abnormalities20
-
Anti-Viral Agents29
-
Viral immune evasion45
-
Complex disease and Pharmogenetics20
-
Immunity to infection: Sequence and timing75
-
Antimicrobial therapies9
-
Hispathology30
