Downs Screening Flashcards
What’s the screening positive rate SPR
Proportion of individuals given a POSITIVE result
What’s the False Negative Rate FNR
Proportion of AFFECTED individuals with a NEGATIVE result
What’s the detection rate DR
Proportion of AFFECTED individuals with a POSITIVE result
What’s the sensitivity
Proportion of AFFECTED people correctly identified as such
Positive people with a positive result
What’s the specificity
Proportion of UNAFFECTED people correctly identified as such
Negative people with a negative result
What’s multiples of medium MoM
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.
What’s the aim of the fetal anomaly screening programme
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
What’s the risk based only on NT or mat age
NT: DR 75-80%. FPR 5%
Mat age: DR 30%. FPR 5%
What other factors affect serum result
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
What screening test is carried out for twin pregnancies and what do you do with NT measurements
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
What are the FASP desired screening detection rates
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%)
What’s tested in the combined test and when’s it taken
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.
What’s tested in the quad test and when’s it tested
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).
What’s the impact of increased sensitivity and specificity on invasive referrals
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
What’s PAPP-A, where’s it produced and when’s it tested
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)
What’s b-hCG, where’s it produced and when’s it tested
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)
What’s AFP, where’s it produced and when’s it tested
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)
What’s uE3, where’s it produced and when’s it tested
Unconjugated oestriol.
Produced by placenta and fetal adrenals, increases with gestational age.
Decreased in T21 (and T13,18, ancephaly, CAH)
What’s Inhibin-A, where’s it produced and when’s it tested
Produced by the placenta. Decreases between 14-17 was, then increases from 17wks.
Tested in 2nd trismester. Optimal sensitivity 16weeks.
Increases in T21
What the false positive rate FPR
Proportion of UNAFFECTED individuals with a POSITIVE result
What’s disorders are screened for in the newborn screening programme
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.
Discuss maple syrup disease.
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.
Discuss homocystiniuria
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
Discuss glutaric acidaemia type 1
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.
Discuss isovaleric acidaemia
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
Discuss newborn baby CF screen
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
Discuss sickle cell testing
AR inherited disorder. Affects rbc. Haemoglobin A (95%): 2 alpha and beta chains.
Screen: high performance liquid chromatography, isoelectric focusing, capillary electrophoresis.
Discuss medium chain acyl-CoA dehydrogenase deficiency MCADD
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.
Discuss phenylketonuria
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.
Discuss congenital hypothyroidism
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.
