Prenatal Testing Flashcards
How prevalent are birth defects in new born children?
(including still births >20 weeks gestation)
**4% of babies have a ‘birth defect’ **
These defects encompass stuctural, functional, genetic, chromosomal and biochemical abnormalities
**4/5 of the most common defects are structural **
Of the chromosomal defects, **trisomy 21 **is the most common autosomal chromosomal defect and Klinefelter syndrome (XXY) is the most common sex chromosome defect (often missed at birth)
What important questions should be asked to ascertain a good family history of inherited diseases?
Ideally, you want to obtain a **three generation family history **- including both first and second degree relatives
Ask questions pertaining to:
- Age of diagnosis of any medical condition
- Inherited conditions
- Down syndrome and other chromosomal conditions
- Other birth defects (eg spina bifida, cleft/lip palate, cardiac defects)
- Intellectual disability
- Recurrent miscarriage
- Unexplained perinatal deaths
- Consanguinity
- Ethnic background (ancestry)
- Need to know about IVF/donor gametes
What does increased risk does maternal age confer in preganancy?
The risk of women having a baby with trisomy 21 increases with maternal age - especially in late 30’s and 40’s
Paternal age can confer increased risk for achondroplasia (autosomal dominant condition resulting in short stature)
Why do pregnant women take folate?
1/500 pregnancies have a neural tube defect
The majority of these can be prevented by taking folate supplements to assist development of the neural tube
Why do people undergo prenatal screening?
Offers reproductive choices
Provides risk information to couples who otherwise would not choose to begin pregnancy (eg because of family history, advanced maternal age)
Gives couple choice of termination of affected fetus
Allows couple to prepare psychologically for birth of affected baby
Helps medical, nursing/midwifery and allied health staff to plan delivery, management and care of affected baby
Provides reassurance when result is ‘normal’
What is the difference between screening and diagnostic tests?
Screening Tests
- All are non-invasive to the foetus
- Identify subsets of women at increased risk of birth defects
- Do not give a definitive result
- Chromosomal, neural tube and genetics most commonly screened
Diagnostic Tests
- Invasive (at the moment)
- Offered to women who indicate an increased risk of birth defect from screening
Explain what is involved in the First Trimester Combined Screening
1) Blood taken at 9-136 weeks (ideally 10 wks)
- 2 biochemical analytes measured
- beta-human chorionic gonadotropin (beta-hCG) and pregnancy associated plama protein A (PAPP-A)
2) Ultrasound performed at 113-136 weeks
-
nuchal translucency measured
- measures level of fluid on the back of a foetus neck- high volume confers risk of non-specific birth defects
- primarily used to identify trisomy 21
- **crown rump length **
- used to date the gestational age of foetus
3) Assessing other factors
* Maternal age etc
Cut off’s for further diagnostic testing:
**T21 = **1/300
T21 = 1/175
Explain what is involved in the Second Semester Prenatal Screening Test
1) Blood taken at 14-20 weeks (15-17 ideal)
- 4 biochemical analytes measured
- beta-hCG, inhibin, oestrodial, alpha-fetoprotein
2) Consideration of other factors
* Maternal age etc
Cut off for diagnostic tests:
- T21 = 1/250
- T18 = 1/200
What is the difference between the **diagnostic **tests chorionic villus sampling and amniocentesis
Chorionic Villus Sampling
From 11 weeks gestation usually
- Samples placental tissue of
- Ultrasound
- Invasive; risk of miscarriage ~1% > background risk
- If termination of pregnancy (TOP) requested, dilatation & curettage (D&C) under general anaesthetic (<16 wks)
Amniocentesis
15-16 weeks gestation usually
- Sample amniotic fluid (~20 ml), containing sloughed off fetal cells removed
- Ultrasound
- Invasive; risk of miscarriage ~0.5% > background risk
- If TOP requested, by prostaglandin induction of labour (>16 wks)
What are three diagnostic tests conducted on the fetal samples?
Fluorescence in situ hybridisation (FISH)
- Fluorescent tags for specific chromosomes during interphase
- Allows you to count chromosomes and identify aneuploides (T21 & T18 etc)
- Is a fast result (within 24 hours) but expensive
Karyotype
- Requires cultured and dividing (metaphase) cells where chromosomes are aligned and counted
- Result take 2 weeks due to culture
- Can observe aneuploides and rearrangements
- Cheaper than FISH
Chromosomal Microarray (CMA)
- Molecular test that determines copy number variation of genes across the entire genome
- Can detect microdeletions and microduplications due to higher resolution than karyotyping
- Can’t detect balanced translocations
What is a Robertsonian Translocation?
Translocations between two ACROCENTRIC (only) chromosomes
Acrocentric chromosomes are 13,14,15,21 and 22
Example of Unbalanced translocation
- between chromosomes 14 and 21 leading to trisomy 21 = 46,XX, der (14;21)+21
Example of Balanced translocation
- between chromosomes 14 and 21 (carrier status) = 45,XX, der (14;21)
When should prenatal molecular karyotyping
be performed?
A “fetal abnormality” is identified on ultrasound scan
The “nuchal translucency” measurement is >3.5mm
A banded (classical cytogenetic) karyotype identifies a complex change
A family member has a microdeletion syndrome and a pregnancy is at risk
How definitive are molecular karyotyping?
Normal result does not exclude genomic abnormality
Presence of small deletion/duplication does not
mean it is pathogenic
Some regions of homozygosity may suggest
autosomal recessive condition and/or consanguinity
Incidental findings
What is non-invasive prenatal testing/scanning (NIPT/S)?
New technologies sample foetal cell free DNA (cfDNA) that originates from placental villus trophoblasst and crosses into the maternal placenta upon apoptosis
- Non-invasive
- Typically around ~10 weeks gestation
- Massively parallel sequencing technology
