Downs Screening

Question 1

What’s the screening positive rate SPR

Answer 1

Proportion of individuals given a POSITIVE result

Question 2

What’s the False Negative Rate FNR

Answer 2

Proportion of AFFECTED individuals with a NEGATIVE result

Question 3

What’s the detection rate DR

Answer 3

Proportion of AFFECTED individuals with a POSITIVE result

Question 4

What’s the sensitivity

Answer 4

Proportion of AFFECTED people correctly identified as such

Positive people with a positive result

Question 5

What’s the specificity

Answer 5

Proportion of UNAFFECTED people correctly identified as such

Negative people with a negative result

Question 6

What’s multiples of medium MoM

Answer 6

Calculation: (serum marker concentration)/(medium concentration value for unaffected pregnancies of the same gestational age).

Used instead of mean as it isn’t skewed by outliers.

Question 7

What’s the aim of the fetal anomaly screening programme

Answer 7

All pregnant women should have equal access to risk calculations for T21,T31,T18 and structural anomalies.

97% of high risk screening results back in 3 working days.

91-93% women with aT21 result choose to terminate

Question 8

What’s the risk based only on NT or mat age

Answer 8

NT: DR 75-80%. FPR 5%

Mat age: DR 30%. FPR 5%

Question 9

What other factors affect serum result

Answer 9

Marker levels: increase in lighter women/ decrease in fatter women/ increase in Afro-Caribbean women.

IVF pregnancies: AFP levels: 10% higher / uE3 levels 10% lower.

Smokers: PAPP-A and hCG levels 20% lower / inhibit levels 60% higher

Question 10

What screening test is carried out for twin pregnancies and what do you do with NT measurements

Answer 10

Quad test (less reliable than for singletons but it’s what NICE recommend).

NT: dichorionic: individual NT measurements.
Monochorionic: risk is based on average of both measurements

Question 11

What are the FASP desired screening detection rates

Answer 11

T21: DR 85%. SPR 1.8-2.5% (1.9-2.4%).

T13,18: DR 80%. SPR 0.1-0.2% (0.13-0.17%).

T21,13,18: DR 80%. SPR 1.8-2.5% (1.9-2.4%).

Quad (T21): DR 80%. SPR 2.5-3.5% (2.7-3.3%)

Question 12

What’s tested in the combined test and when’s it taken

Answer 12

1st trimester: 11+2-14+1wk. CRL 45.0-84.0mm.

b-hCG (increased for T21).
PAPP-A (decreased for T21).
NT over 3.5mm.

Question 13

What’s tested in the quad test and when’s it tested

Answer 13

2nd trimester: 14+2-20+0wks (done for late attenders).

AFP (decreased in T21).
b-hCG (increased in T21).
uE3 (increased in T21).
Inhibin A (increased in T21).

Question 14

What’s the impact of increased sensitivity and specificity on invasive referrals

Answer 14

Reduction of invasive referrals over the last 10yrs.

Shift from AF to CVS with 1st trimester screens.

Invasive now for mat anxiety, abn scan, screen risk, increased NT

Question 15

What’s PAPP-A, where’s it produced and when’s it tested

Answer 15

Pregnancy associated plasma protein A.

Originates from syncytiotrophoblasts, produced solely by the fetus and increases with gestational age.

Tested in 1st trimester

Decreased in T21 (and T13,18)

Question 16

What’s b-hCG, where’s it produced and when’s it tested

Answer 16

b subunit of human chorionic gonadotropin.

Hormone produced by syncytiotrophoblasts, reduces with gestational age.

Tested in 1st and 2nd trimester.

Increases in T21 (decreases in T13,18)

Question 17

What’s AFP, where’s it produced and when’s it tested

Answer 17

Alpha fetoprotein.

Produced by yolk sac and liver, in responses with gestational age.

Tested in 2nd trimester.

Decreases in T21 (and hydatidiform moles/fetal demise)

(Increases in neural tube defects (spina bifida), GI, renal defects, cystic hygroma)

Question 18

What’s uE3, where’s it produced and when’s it tested

Answer 18

Unconjugated oestriol.

Produced by placenta and fetal adrenals, increases with gestational age.

Decreased in T21 (and T13,18, ancephaly, CAH)

Question 19

What’s Inhibin-A, where’s it produced and when’s it tested

Answer 19

Produced by the placenta. Decreases between 14-17 was, then increases from 17wks.

Tested in 2nd trismester. Optimal sensitivity 16weeks.

Increases in T21

Question 20

What the false positive rate FPR

Answer 20

Proportion of UNAFFECTED individuals with a POSITIVE result

Question 21

What’s disorders are screened for in the newborn screening programme

Answer 21

Phenylketonuria.
Congenital hypothyroidism.
Sickle cell anaemia/disease.
Cystic fibrosis.
Medium chain acyl-CoA dehydrogenase deficiency.
Maple syrup urine disease.
Homocystinuria(pyridoxine unresponsive).
Glutamic academia.
Isovaleric acidaemia.

Question 22

Discuss maple syrup disease.

Answer 22

AR condition. Defects int he branched chain 2-keto acid dehydrogenase complex. Accumulating of leucine, iso-leucine, allo-leucine and valine.

Catastrophic illness very early in newborn period.
Screen: MS/MS quantifies amount of leucine, iso-leucine, allo-leucine and valine. Elevated levels is suggestive of MSUD.

Question 23

Discuss homocystiniuria

Answer 23

AR condition. Defect in the catabolism of methionine caused toxic accumulation of homocyteine.

Classic form: skeletal, ocular, vascular, nervous system pathology: untreated: poor prognosis.

50% pts: responsive to pyridoxine (the unresponsive are detected by this screen)

MS/MS quantification of methionine and total homocysteine levels

Question 24

Discuss glutaric acidaemia type 1

Answer 24

AR disease. Defective catabolism of certain a causing toxic accumulation of glutaric acid and related compounds, particularly lysine and tryptophan.

Microcephaly, neurological/metabolic crises.

MS/MS: quantify glutarylcarnitine.

Question 25

Discuss isovaleric acidaemia

Answer 25

AR disease. Defective catabolism of leucine causes toxic accumulation of isovaleric acid and its glycine and carnitine derivatives.

Failure to thrive, dev del.

MS/MS: isovalerylcaritine levels

Question 26

Discuss newborn baby CF screen

Answer 26

Initial screen detects increased levels of IRT immunoreactive trypsinogen at 5 days.

Look for 4 most common mutations associated with severe disease. If 1 or 2 mutations founds: further testing

Question 27

Discuss sickle cell testing

Answer 27

AR inherited disorder. Affects rbc. Haemoglobin A (95%): 2 alpha and beta chains.

Screen: high performance liquid chromatography, isoelectric focusing, capillary electrophoresis.

Question 28

Discuss medium chain acyl-CoA dehydrogenase deficiency MCADD

Answer 28

Inherited AR. Problems breaking down fats to energy for the body causes build up of medium-chain fatty acids (C8)

Serious illness/death.

MS/MS: measure C8 levels. If positive: mutation screening: c.985A>G ACADM 88% cases.

Question 29

Discuss phenylketonuria

Answer 29

AR. Defects in phenylalanine hydroxyl are enzyme (metabolises phenylalanine and tyrosine) leads to toxic accumulation of phenylalanine build up.

Effected seen at 6mnths. Serious, irreversible mental disability.

MS/MS (tandem mass spectrometry): quantify absolute conc of Phe and Tyr and their ratios.

Question 30

Discuss congenital hypothyroidism

Answer 30

Inborn error of metabolism. Thyroid fails to produce thyroxine.

Serious permanent physical and mental disability.

PAX8 and TSHR nuts disrupt normal thyroid devpt.

Screening: thyroid stimulating hormone levels.