prenatal diagnosis

Question 1

what are the benefits of prenatal screening and diagnosis?

Answer 1

parental reassurance
prenatal diagnosis may allow women to undertake a pregnancy they might not have otherwise undertaken
if abnormality detected =
increased parental options -> further testing, referral, counselling (plan for birth or termination), preparations for special needs child
altered obstetric management
facilitated neonatal management

Question 2

what are the risks of prenatal screening and diagnosis?

Answer 2

parental anxiety - false positive, true positive
pregnancy complications
pregnancy loss

Question 3

what are the current screening methods?

Answer 3

integrated prenatal screening = nuchal translucency, PAPP-A, hCG, AFP, uE3, inhibit A
first trimester screening (combined) = NT, hCG, PAPP-A
quadruple maternal serum screening = hCG, AFP, uE3, inhibit A

Question 4

what is nuchal translucency?

Answer 4

subcutaneous fluid filled space located between back of fetal neck and skin
measured on US between 11-13+6 measurement is not vaild outside this period
NT increases with gestational age
if >3.5mm = diagnostic testing indicated
associated with = trisomy 21,18,13, triploidy and turners syndrome, spontaneous fetal loss

Question 5

what are the methods of chromosomal evaluation?

Answer 5

non-invasive = fetal cells from maternal blood, preimplantation embryos (PGD) 
invasive = amniotic fluid (amniocentesis), placenta (chorionic villus tissue), fetal blood

Question 6

how is amniocentesis performed?

Answer 6

percutaneous 
20-23g needle 
US guided 
usually 20cc fluid 
results 2-3 weeks

Question 7

what are the complications of amniocentesis?

Answer 7

pregnancy loss - 0.3-1% 
increase risk = if larger needle, multiple needle insertion, discolouration of fluid, high AFP, placental perforation 
leakage of amniotic fluid 
amnionitis 
vaginal bleeding 
needle puncture of fetus

Question 8

how is CVS performed?

Answer 8

percutaneous transabdominal with 19-20g needle

Question 9

how s CVS analysis performed?

Answer 9

direct analysis examines the trophoblast cells of the placenta, results in few hours, greater vulnerability to mitotic error
cultured analysis = examines the fibroblast like cells of the villi stroma 10-14 days, accurately reflect the chromosomes of fetus

Question 10

what is mosaicism?

Answer 10

true chromosomal mosaicism is when 2 or more abnormal cell lines are detected in 2 or more cultures from the same individual
psuedomosaicism is a term used to describe 2 abnormal cell lines that are found in only one culture

Question 11

what are the 4 possible conditions of mosaicism?

Answer 11

1 - mosaicism only in placenta not affecting the fetus or placental function
2 - mosaicism only in the placenta not affecting the fetus but alter placental function
3 - trisomy cells are both in the placenta and in the fetus
4 -trisomy cells in the placenta and uniparental disomy in fetus

Question 12

when does uniparental disomy occur?

Answer 12

when individual inherits 2 copies of a chromosome pair from 1 parent and no copy from the other parent

Question 13

how does uniparental disomy occur?

Answer 13

loss of chromosome from a trisomy zygote = triatomic rescue
duplication of chromosome from monosomic zygote = monosomic rescue
fertilisation of gamete with 2 copies of a chromosome by a gamete with no copies of the same chromosome = gamete complementation

Question 14

what are the health concerns in uniparental disomy?

Answer 14

parental imprinting in the case of heterodisomy and isodisomy
unmasking of recessive conditions in some cases of isodisomy

Question 15

what is non-invasive prenatal testing?

Answer 15

single blood test that uses cutting edge technology to screen pregnant women for chromosome problems as early as 10 weeks

Question 16

which patients can be offered non-invasive prenatal testing?

Answer 16

maternal age related risk
positive results on maternal serum screening
abnormal ultrasound findings
prior pregnancy with aneuploidy
parental robertsonian translocation involving one of the tested chromosomes

Question 17

what are the aims of non-invasive pre0natal testing?

Answer 17

reduce exposure of fetus to risk
reduce false positives
enables high detection rate
testing that can easily be offered to all pregnant women

Question 18

what are the 2 sources of fetal DNA?

Answer 18

fetal cells = require isolation via mechanical/biochemical means
cell free DNA = maternal blood contains both maternal and fetal cfDNA

Question 19

how does fetal cell-free DNA get into maternal blood?

Answer 19

released through apoptosis - likely arises from cytotrophoblastic cells of placenta
released into bloodstream as small DNA fragments
reliably detected after 7 weeks gestation
undetectable within hours postpartum

Question 20

how are cell free DNA analysed?

Answer 20

fetal DNA fragments in maternal blood -> cell free DNA fragments are then sequenced -> compare the individual sequenced chromosomes against a reference for analysis

Question 21

what are the advantages and disadvantages of NIPT?

Answer 21

+ve
reduces unnecessary procedures in borderline high risk women
can give more equivocal risk assessment than any other options offered on NHS

-ve 
currently not available on NHS 
costly 
still classified as screening not diagnostic 
takes 7-10 days