Congenital Abnormalities And Their Identification

Question 1

What is a screening test?

What makes a good screening test?

Answer 1

Available for all women
Gives a measure of risk of fetus being affected by particular disorder
A higher risk pt is offered a diagnostic test
E.g. Risk of down syndrome- 1 in 50 pregnancies

Cheap
High sensitivity- does not miss affected individual
High specificity- not many false +ves
Safe

Question 2

What is a diagnostic test?

Whats an acceptable diagnostic test?

Answer 2

Performed in women w/ high risk to confirm or refute the possibility .
Implications of being affected by the condition should be serieous to warrant the test.m

Not always offered as 1st line tx
Expensive
Or
Sign complications

High risk- impact minimized.

Question 3

Whats sensitivity?

Answer 3

Proportion of subjects w/ condition classified by test as screen +ve.

Question 4

Whats the negative predicting value?

Answer 4

NPV- is the probability that the subject who is screen -ve will not have the condition.

Question 5

Whats specificity?

Answer 5

Ppl w/o condition who are screened as negative

Question 6

Whats the screen +ve rate?

Answer 6

Proportion of subjects who are classified as high risk by the test.

Question 7

Whats the Positive Predictive Value?

Answer 7

PPV- probability that proportion of people who’s screen +ve will have the condition.
In practise, PPV is low, most screen +ves do not have the condition…. Rate is similar to FPR

Question 8

What is the false positive rate?

Answer 8

FPR- ppl classified as high risk who do not have the condition.

Question 9

What is the Maternal blood testing?

Methods of prenatal testing for congenital abnormalitites

Answer 9

As a screening test:
Neural tube defects- a- fetoprotein( AFP)- product of fetal liver. When fetus has open neural tube defect (NTD) /gastrochisis- maternal levels are raised. Or indicate higher risk of 3rd trimester complications
USS is more accurate
Chromosomal: some maternal markers altered;
B-hCG, pregnancy associated plasma protein A (PAPP-A) , AFP, oestriol, inhibin.
Assc w/ maternal age + USS measurments.

Question 10

Maternal blood testing as a diagnostic test, what does it do?

Answer 10

Just fetal gender still - few fetal cells in maternal blood will revolusionise prenatal diagnosis in future

Question 11

Why is the USS used?

Answer 11

To:
1. Confirm gestation- transvaginal scan, pregnancy site and exlude multiple pregnancy.
2. Cornerstone for screening for trisomies
A. Nuchal translucency - space b/w skin & soft tissue overlying cervical spine betwwen 11-14 weeks is measured. The larger it is the higher the risk.
Esp- structural- cardiac abnormalities, exopthalmos !!
3. To aid other diagnostic tests- amniocentesis and chorionic villus sampling (CVS) are performed under USS vision.
4. As a diagnostic test. 18-21 weeks- anomaly scan for struct. Abn. Congenital malformations of all organs & systems are detectable. 25% abn detectable in 11-14 week. Cardiac.. 20 weeks.

Question 12

Whats fetal magnetic resonance imaging?

Answer 12

MRI- scan for fetus in utero- diagnosis of intracrania lesions
Better at differentiating diff types of tissue.

Question 13

Whats thw 3-D/4-D USS?

Answer 13

Reconstructs 3-D images, tertiary referral centres.

Question 14

Whats amniocentesis?

Answer 14

Diagnostic test- removal of amniotic fluid- fine-gauge needle under USS guidance.
Safe from 15 weeks
Allows for prenatal diagnosis of chromosomal abn, some infx- cytomegalovirus(CMV) & toxoplasmosis & inherited disorders- sickle cell anaemia, thalassaemia, CF.

Question 15

What % of women miscarry after amniocentesis?

Answer 15

1%

Question 16

Whats chorionic villus sampling?

Answer 16

Diagnostic test- biopsy of the tropgoblast, fine-gauge needle through the abdo wall or cervix and into the placenta, after 11 weeks.

Its used ro diagnose chromosomal abn & autosomal dominant and recessive conditions.

Question 17

What are the advantages of Chorionic villus sampling?

Answer 17

Diagnosis faster than amniocentesis, allows abnormal fetus to be identified at a time for abortion- if requested- under general anaesthesia.

Question 18

Why are miscarry rates for CVS higher?

Answer 18

Miscarriage rates are higher- cz its performed earler when spontaneous miscarriage is still common + cz its a more diff procedure.

Question 19

How do we diagnose the abn after sampling?

Answer 19

FISH- flurescence in situ and PCR- poly,erase chain rct ysed to diagnos abn in less than 48hrs.

Question 20

What are preimplantation genetic disorders?

Answer 20

In vitro fertilization(IVF) allows cells from a developing embryo to be removed for analysis before the embryo is transferred ro the uterus.
Expensive techniques- ethical dilemmas.
Has been used in sex-linked disorders, trisomies, both autoaomal dominant and recessive disorders.
Even if couples are fertile.

Question 21

What are some chromosomal abnormalities?

Answer 21

6/1000 live births. Most- trisomies.
Down’s syndrome-
Nuchal scan- aneuploidy, pregn dates.
Trisomy 18- Edwards syndrome
Trisomy 13- patau’s syndrome - also common w/ ⬆️ maternal age.
Affected fetus dies in utero or shortly after birth.

Sex chromosome abn- klinefelter’s syndrome-47XXY- males- normal intelect, small testes, infertile.
Turner’s syndrome- X0- single X chro osome- female, infertile , normal intelect.

Question 22

What is downs syndrome?

Answer 22

trisomy 21- usually random non-dysfuntional meiosis.
Common w/ advanced maternal age.
Mental retardation, characteristic faces and often (50%) congenital cardiac disease.

Question 23

What are some RFs for Downs?

Answer 23

Hx- ⬆️ maternal age, px affected baby ⬆️ risk by 1%, balanced parental translocation- rare

USS- thickened nuchal translucency, struct. Abn., abscent or shortened nasal bone, tricuspid regurgitation.

Blood tests: 
Low PAPP-A (1st trimester)
⬆️⬆️ b-hCG (1st/2nd trimester) 
⬇️AFP (1st/2nd trimester)
⬇️ oestriol -2nd
⬆️ inhibin -2nd

Screening test- 75% sensitivity 3% Fositive rate

Question 24

Whats the combined test,

Answer 24

Screening test + PAPP-A + b-hCG bloods, + nuchal translucency by USS measurments in 11-13 + 6 weeks

Question 25

Whats the triple test?

Answer 25

Blood test at 16 weeks- AFP, hCG and oestriol
Less accurate.
No nuchal translucency- USS- less esxpensive.

Question 26

What are some congenital abnormalities?

Answer 26

2% of pregnancies
Can be:
Structural deformities- diaphragmatic hernia
Chromosomal: esp trisomies- downs
Inherited diseases- Cystic fibrosis
Or result od intrauterine infx- rubella
Drug exposure- antiepileptics 

25% perinatal deaths + disability in later life
Counselling must be non-directive