1. Screening What do you already know? What types are there? What does it mean? Who is it for? Examples?

2. Learning Outcomes Compare and contrast the two screening types Examine the tests and techniques used to monitor pregnancy and developing fetus.

3. Antenatal and Postnatal Screening A variety of techniques can be used to monitor the health of the mother and developing fetus. Antenatal (pre-birth, in pregnancy) screening identifies the risk of a disorder so that further tests and a prenatal diagnosis can be offered. Postnatal screening is after birth screening which can diagnose metabolic or genetic disorders in the baby.

4. Antenatal Screening Antenatal screening can be separated by technique, there are 5 we will concentrate on; 1.Antenatal care (general health checks) 2.Ultrasound 3.Biochemical marker tests 4.Diagnostic Testing 5.Rhesus antibody testing

5. The general health of the mother is monitored (with consent) including; -Blood (full blood count, iron levels, also including sickle cell anaemia, ß- Thalassaemia) -Urine tests (infections, calcium levels) -Blood pressure (pre-eclampsia potential if hypertension (high BP) -Blood type (blood group antibodies can affect baby or for potential blood transfusion) -Weight / Height (risks only if BMI is greater than 30) Antenatal Screening; Care

6. Antenatal Screening; Ultrasound Bounce off the fetus, image on screen. 8-14 weeks – dating scan, where they measure and come up with EDD(estimated date of delivery) High frequency (20,000 mHz) Sound waves

7. Mothers skin Foetus Pre-natal ultrascans Image probe Gel

8. depth Echo location Depth 9.1 cm distance= speed X time depth = distance /2 Piezoelectric crystal

9. Imaging Image

10. 4 weeks 8 weeks 12 weeks 16 weeks 20 weeks 24 weeks

11. 28 weeks 32 weeks 36 weeks 40 weeks

15. An anomaly scan at 18-20 weeks may detect serious physical problems. Organs are checked with location as well as measurements of femur etc. Antenatal Screening; Ultrasound

16. Antenatal Screening; Biochemical Tests Medical conditions can be detected by a range of marker chemicals that indicate a condition but need not necessarily be directly part of the condition. Examples such as HCG levels and protein levels. Describe the relationship between gestation in both normal and Trisomia 21 for; a.HCG levels b.PAPP-A levels

17. Antenatal Screening; Biochemical Tests HCG – Trisomy 21 (Down Syndrome) increases and peaks at 8 in weeks 12-14, then decreases at weeks increase. This is double the normal peak at 20 weeks of 4. which then decreases slower, and remains higher than the Trisomy 21. PAPP-A (Pregnancy-Associated Plasma Protein A) for normal graph increases as weeks increases until peaks at 10 weeks at approximately 18 then steadily declines. Whereas Trisomy 21 increases and weeks increase to 10 later at 16 weeks, then it steadily decreases but consistently remains higher than normal.

18. Antenatal Screening; Biochemical Tests Thus proving that biochemical tests MUST be used in CONJUNCTION with DATING SCAN as marker chemicals vary normally during pregnancy. Measuring a substance at the wrong time could lead to a false positive result! Look at appendix 4- p357 DiagnosisResult False PositiveHave condition False Negative

19. Antenatal Screening; Diagnostic Testing As a result of routine screening or for individuals in high risk categories or medical history, further tests may be offered. Diagnostic tests are usually definitive but require an examination of the karyotype* of the fetus cells. The chromosomes will be staining and visualising the cells under microscope. NB Genotype refers to the genetic make up of an organism. Phenotype are the physiological appearance. *Karyotype refers to the number of structure of chromosomes in an organism

20. Antenatal Screening; Diagnostic Testing To gain the cells needed there are two methods; Amniocentesis Chorionic Villus Testing/ Sampling In deciding to proceed with these tests, the element of risk will be assessed (high/medium) as will the decisions the individuals concerned are likely to make if a test is positive.

23. Antenatal Screening; Diagnostic Testing

24. Compare these using a double bubble Amniocentesis vs. Chorionic villus sampling Similarities Differences

25. Genetic Testing Chorionic Villi Sampling Karotyping immediately Earlier (8-10(up to12) weeks) Takes 20 mins 2% miscarriage risk Results not 100% reliable Amniocentesis Test Cells cultured then stained 10-12 (up to 18) weeks Very small risk of infection 0.5% miscarriage risk Results not 100% reliable

26. Doctor Diagnosis – have a look at these karyotypes, what is your diagnosis? 1 2 3 4

27. 56 8 7

28. Doctor Diagnosis... Answers 1.Trisomy 21 Down Syndrome 2. X only – Turner Syndrome 3.Normal female 4. Hard to see – microdeletion of 22 – Digeorge 5.Extra X – Klinefelters syndrome 6.Trisomy 18 – Edwards syndrome 7. Normal male 8.Triple XXX Like 4, shorter deletion Chromosome 5 (Cri-du-Chat)

29. Down’s syndrome: how does it happen? Chromosomal non-disjunction during meiosis of eggs and sperm. 1. Chromosomes replicate 2. Homologous chromosomes separate 3. Chromatids from each chromosome separate

30. Antenatal Screening; Rhesus Antibody Testing Blood type – what is it? Antigens – surface glycoprotein molecules on cells RBC has either A, B or Rh antigen If no A or B – called O Rh present = + if absent = -

31. Antenatal Screening; Rhesus Antibody Testing Antigens on the surface of molecules complex with antibodies (Y shaped molecules) Antigens show whether the surface is “foreign” to the circulating antibodies. This can cause problems in transfusions.

32. Antenatal Screening; Rhesus Antibody Testing Agglutination, clumping causes problems. When a pregnant blood should not mix, however during delivery they can mix. This causes “sensitisation” – similar to vaccination. Thus subsequent pregnancies could be rejected.

33. Rhesus Antibody Testing The antigens on the surface on the RBC is determined by parents – used for paternity testing before DNA! So an injection of Anti-D given as soon as birth to prevent binds foetal RBCs carrying the rhesus antigen and prevents the mother producing antibodies against it.

34. Demonstrate your understanding Case study of Familiar Downs Syndrome p140, 143 and 145 Come up with a timeline for diagnosing Down Syndrome for an anxious first time mother who is 47 years old.

35. Downs Syndrome. 1.Medical history – 47 age risk increased 2.Biochemical screening test HCG/PAPP-A (weeks 10-14) 3.Alpha-fetoprotein screening – higher risk 4.Nuchal translucency test on ultrasound (11-14 weeks) – not diagnosis only higher risk! 1-4 are called combined testing – as more than one indicator 5. Amniocentesis or Chorionic Villus Sampling testing allowing karotype ; diagnosis test!

36. Review – testing your knowledge 1.What is meant by term antenatal screening? 2.a. At approximately what stage in pregnancy are these performed? i.Dating scan ii.Anomaly scan b. What is the purpose of these scans? c. What is the name given to the technique used to obtain these scans 3. Distinguish clearly between screening test and diagnostic test. 4. Give two differences between amniocentesis and chorionic villus sampling? 5. When does a women need to take anti-Rhesus antibodies?