7. Prenatal Screening Flashcards
How many babies are born/year
70,000
What percentage of babies have birth defects
4%
What kind of birth defects exist?
Structural Functional Genetic Chromosomal Biochemical
What is the most common chromosomal abnormality?
Trisomy 21 (1 in 600 ~ 1 in 1000) 2nd most common XXY (Klinefelter syndrome)
What information is important from taking a family history?
- Should ask a 3 generation family history Including age of diagnosis
What questions should you ask when taking family history?
- Inherited conditions - Down syndrome and other chromosomal conditions - Other birth defects, e.g. spina bifida, cleft/lip palate, cardiac defects, intellectual disability - Recurrent miscarriage - Unexplained perinatal deaths - Consanguinity - Ethnic background - IVF/Donor gametes
What is the risk of giving birth to a child with Down Syndrome?
Increases exponentially from 1 in 1411 at age 20-24 to 1 in 32 at age 45
What is the prevalence of neural tube defect?
1 in 500 o Spina bifida o Anencephaly o Encephalocele - Folate Should be taken before and during pregnancy
What are the benefits of prenatal testing?
- Offers reproductive choice - Risk information - Choice of termination - Prepare psychologically - Help plan delivery and management - Provide reassurance
What are the 2 major types of prenatal testing?
Screening test - Offered to all pregnant women - Non-invasive - Taken by up to 80% pregnant women Diagnostic tests - Offered to women who are at increased risk of having a child with a birth defect - Invasive
What is the 1st trimester combined screening?
- Blood taken at 10 weeks o 2 biochemical analytes measured - Ultrasound performed at 11 -13 weeks. o Nuchal translucency measured (oedema that occurs behind fetal neck) o Crown rump length (dating) - Other factos including maternal age Results/Cutoff - T21: 1 in 300 - T18: 1 in 175 Detection rate for T21 is 93% - 4.6% false positive result
What is the 2nd trimester combined screening?
- Blood taken at 14-20 weeks (15-17 ideal) o 4 biochemical analytes measured - Maternal age Cutoff - T21 1 in 250 - T18 1 in 200 - Neural tube defects >2.0MoM Detection rate for T21 is 85%, with 6.5 false positive rate Detection rate for neural tube is 93% but ultrasound is recommended
What is NIPT/S?
(non-invasive prenatal testing/screening) – using Cell-free fetal DNA/RNA in maternal blood - Non invasive - ~10 weeks gestation - Uses new sequencing technology
What does Chronic cillus sampling (CVS) involve?
- From 11 weeks gestation - Placental tissue - Ultrasound - Invasive 1% miscarriage - If termination of pregnancy requested, dilation & curettage under general anaesthetic (
What is Amniocentesis?
15-16 weeks gestation
Amniotic fluid (20ml) containing sloughed off fetal cells removed
Ultrasound
0.5% miscarriage
If TOP requested, by prostaglandin (>16 wks)
What is fish?
- Fluorescence in site hybridization
- Using probes on interphase cells to look for abnormalities in chromosome numbers
What recessive conditions often present without a Fx?
- Haemoglobinopathies (1 in 20 – ethnicity)
- Ashkenazi jewish panel (7 conditions, 1 in 25 to 1 in 100)
- CF (1 in 25 – Northern Europe)
- Spinal muscular atrophy (1 in 40)
- Fragile X syndrome (1 in 200)
What is Robertsonian translocation?
Rearrangement on Acrosomic Chromosomes
What re acrocentric chsomosomes?
Chromosomes with a small P arm
Examples (13, 14, 15, 21, 22)
Balanced vs unbalanced translocation in Trisomy 21
- Most common is 14;21
- If they are balanced, has not loss any genetic material it will not cause any problems for the individual but may cause problems for offspring when inherited
- Balanced translocation = carrier status and that will have no implication to individual unless genetic information has been lost
But it can occur in the offspring - Unbalanced translocation between chromosome 14 and 21 leads to trisomy 21 = Down Syndrome
How does unbalanced translocation cause Down Syndrome?
Microarrays (DNA chips)
- DNA sequences and/or gene expression
- Can look at SNPs
- Can look at larger changes – number of chromosomes and copy number variations
What are chromosomal microarrays?
- Array CGH (comparative genome hybridization) and SNP arrays
o Also called molecular karyotyping - Probes (25 base oligonucleotides along entire genome)
- Variable resolution
- For deletions and microdeletions
When should prenatal molecular karyotyping be performed?
- a fetal abmormality identified on ultrasound scan
- Nuchal translucency is >3.5mm
- A banded (classical cytogenic) karyotype identifies a complex change
- A family member has a microdeleton syndrome and a pregnancy is at risk
What dooes the result of molecular karyotyping show?
- Normal result does not exclude genomic abnormality
- Presence of small deletion/duplication does not mean pathogenic
- Some region of homozygosity may suggest autosomal recessive condition and/or consanguinity
- Incidental findings
What is pre-implantation genetic diagnosis?
- Require IVF
- One or two cell from 3 day old dividing zygote
Can do DNA testing, FISH, now chromosomal microarrays
What are the analytes in the second trimester maternal serum screening test? and what indicates an increased risk of Trisomy 21
- a-fetoprotein (Reduced)
- Oestriol (Reduced)
- hCG (Increased)
- Inhibin A (Increased)
What are the analytes taken in the first trimester?
- hCG
- PAPP-A
If both are reduced = Increased Risk of Tri18
If hCG is increased and PAPP-A is reduced = Increased risk for Trisomy 21
