Invasive Procedures For Prenatal Diagnosis

2. Invasive Procedures For Prenatal Diagnosis Dr. RahimiSharbaf Tehran University of Medical Science Women (Mirzakochak Chan) Hospital

3. PRINCIPLES Diagnosis of fetal chromosomal defects requires invasive testing. Type of procedure depend on many factors: indication, GA, how soon result • Chorionic Villus Sampling (C V S) • AMNIOCENTESIS • Fetal Blood Sampling (CORDOCENTESIS) • Fetal Tissue Biopsy BASICS ARE THE SAME

4. Indications for Invasive Prenatal Diagnosis • Positive prenatal screening test( most common) [NON INVASIVE TEST] • Increased NT • Previous child with chromosome abnormalities • Parent with chromosome abnormality • Fetal anomaly suspected/diagnosed on ultrasound or IUGR • DNA diagnosis: single-gen disorder, x-linked disorder • Metabolic disorders • Family history of chromosome abnormality

5. Current evidence suggests thatnon-invasive prenatal testing • Cell-free DNA analysis in maternal plasma • Has the potential to significantly reduce the number of invasive procedures • – Is not diagnostic for the time being • Down syndrome detection rate 98.6% (209/212), false-positive rate 0.20% (3/1371) • Not recommend for low risk & multiple pregnancy

6. The median and 95thcentile of NT at a CRL of 45 mm are 1.2, and 2.1 mm and the respective values at CRL of 84 mm are 1.9 and 2.7mm • The 99th centile does not change significantly with CRL and it is about 3.5 mm.

7. Relation between Nuchal Translucency thickness and prevalence of chromosomal defects • <95th centile 0.2% • 95th–99th centiles 3.7% • 3.5–4.4 mm 21.1% • 4.5–5.4 mm 33.3% • 5.5–6.4 mm 50.5% • ≥6.5 mm 64.5%

8. In 2007 ACOG guideline • Not specific age for invasive testing • Elect invasive testing directly

9. Multiple Pregnancy In multiple pregnancies prenatal diagnosis of chromosomal abnormalities is complicated because: Firstly: the techniques of invasive testing may provide uncertain results or may be associated with higher risks of miscarriage Secondly: the fetuses may be discordant for an abnormality, in which case one of the options for the subsequent management of the pregnancy is selective fetocide

10. Multiple Pregnancy • Should perform only in a fetal medicine unite • First trimester chorionicity should be determine • In monochorionic a single amniocentesis may reasonable unless discordance in fetal abnormality or growth

11. Multiple Pregnancy • In pregnancies discordant for chromosomal defects the main options are either selective fetocide or expectant management. • Selective fetocide after 16 weeks of gestation is associated with three-fold increase in risk of spontaneous abortion compared to reduction before 16 weeks.

12. Amniocentesis OR cvs in twins • Amniocentesis is effective in providing a reliable karyotype for both fetuses and the procedure-related fetal loss rate is about 2%. • In the case of chorionic villus sampling, the procedure-related fetal loss rate is about 1%, but in about 1% of cases there may be a diagnostic error, either due to sampling the same placenta twice or cross contamination. • The main advantage of chorionic villus sampling is that it provides results sufficiently early to allow for safer selective fetocide.

13. Invasive Procedures in Hepatitis B & C & HIV • Use noninvasive method • Every effort to avoid transvercing placenta • IN HIV if mother is not on antiretroviral therapy and if a fetal needle-stick occurs risk of vertical transmission increase

14. Post Procedure Consideration • Should be shown Fetus and fetal heart activity • Resume normal activity • Defer sexual activity for 24-48 • Report=> persistent uterine activity, vaginal bleeding, leakage AF or fever • Injection RhIG in at risk Rh neg ( 300µg)

15. Complication • Fetal loss rate: Combination of procedure-related loss +background loss • Most procedure-related loss occur within 2 weeks • procedure-related loss => gestational age, operative experience, type of procedure

16. Chorionic Villus Sampling

17. Chorionic Villus Sampling • Is the only available method for prenatal diagnosis in the first trimester • CVS, or placental biopsy perform from 11 weeks & therafter • CVS usually perform transabdominally • Some use transcervical technique ( 2% ) • over last few years CVS use increase=> in some country more than 50% diagnosis of chromosomal abnormality

18. Invasive Procedures For Prenatal Diagnosis & Treatment Mirza Kochak Khan Hospital – 1386-87 1386 1387 • CVS 276مورد 200 • آمنيوسنتز 254 مورد 385 • كوردوسنتز 71 مورد 38 • IUT 66 مورد 45

19. Chorionic Villus Sampling • A 18-20 gauge spinal needl Advantage: • Diagnosis in first trimester & rapid diagnosis • Termination in pregnancy easier and safer • Pregnancy less obvious, more private • May be less bonding • One major different with Amniocentesis is AFP for NTD

24. CVS - Complications • Fetal loss no greater than amniocentesis in experience hand • Ambiguous results/maternal cell contamination ~1-2% • Culture failure 1-2% • Placental mosaicism ~ 1%

25. Factors Affecting Rate ofFetal Loss Following CVS • Experience of operator • Number of attempts • Manipulation required • Route of CVS(TA-CVS preferable) Who Report 1991

26. the consensus of the modern literature is that in experienced hands there is little to no ifferences between the procedure risks of amniocentesis and chorionic villus sampling. However, is clearly that CVS harder to learn and has a steeper learning curve

27. AMNIOCENTESIS

28. AMNIOCENTESIS • First perform in 1950 • Contain amniocytes, & fetal cell from skin, GU system, gut & biochemical pruducts • Most widely used prenatal diagnostic invasive procedure • Every genetic condition diagnosis able through fetal tissue has been made in amniotic fluid

29. Indication • Choromosal analysis • DNA diagnosis: single-gen disorder, x-linked disorder • Biochemistry: a-fetoprotein, acetylcholinsterse • Fetal infection • Choroamninitis • Lung maturation

30. Advantages of Mid-Trimester Amniocentesis • Large National Experience • Lab Techniques Standardized • Readily Available • Very Safe • Very Accurate • Time to ready answer

31. AMNIOCENTESIS • Gestational age ( 16-20w) –{Early amniocentasis} • Comprehensive ultrasound evaluation • Placenta position • Amniotic fluid location • Number of fetus

32. AMNIOCENTESIS • A 20-22 gauge spinal needle • Avoid fetus cord & placenta( if possible) • Continues visualization of the needle avoid: Bloody AF Dry taps Need for multiple insertion • 15-20 ml AF (first 1-2 ml discarded) • Bloody Amniotic Fluid(maternal origin) dose not adversely affect culture • Brown AF & dark red & wine colored AF=> increased poor pregnancy outcome

33. AMNIOCENTESIS Problems • Fetal Loss 1/400 or less • Minimal fluid leakage <1.0% • Culture Failure 0.5% • Pseudomosaism <0.5%

36. Mean amniotic fluid volume during normal pregnancy These values represent the 50th percentile. There is considerable variability around the mean. The 5th, 50th, and 95th percentiles at 33 weeks of gestation are approximately 300, 800, and 1900 mL, respectively. Data from: Brace, RA, Wolf, EJ, Am J ObstetGynecol 1989; 161:382.

37. 40 ml 100 ml 185 ml 12 weeks 14 weeks 16 weeks

38. PercutaneousUmbilical Cord Blood Sampling (PUBS)

39. Fetal Blood Sampling (FBS) • First was report three decades ago • Was first performed under fetoscopic guidance • Use for diagnosis & treatment

40. Fetal Blood Sampling • Rapid karyotype • Abnormal ultrasound in second & third trimester • Clarify chromosome mosaicism in amniocetesis or CVS • Assess fetal Hb

41. Fetal Blood Sampling • Perform from 18w • 20-22 gauge needle • Sample site • Cardiocentesis

44. Fetal Blood Sampling complication • Hemorrhage • Fetal bradycardia ( most common), fetal monitor at least for 30 minate • Intrauterin infection • Fetal loss ~1% ( 0.2%)

45. Thank you for attention