Invasive Procedures For Prenatal Diagnosis

Dr. Rahimi SharbafDr. Rahimi Sharbaf

Tehran University of Medical Science Tehran University of Medical Science

Women (Women (Mirza kochak ChanMirza kochak Chan) Hospital) Hospital

PRINCIPLESDiagnosis 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)AMNIOCENTESISFetal Blood Sampling (CORDOCENTESIS)Fetal Tissue Biopsy

BASICS ARE THE SAME

• 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

Indications for Invasive Prenatal Diagnosis

Current evidence suggests thatnon-invasive prenatal testing

Cell-free DNA analysis in maternal plasmaHas 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

The median and 95th centile 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 2.7 mm

The 99th centile does not change significantly with CRL and it is about 3.5 mm.

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%

In 2007 ACOG guidelineNot specific age for invasive testing

Elect invasive testing directly

Multiple PregnancyIn 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

Multiple PregnancyShould 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

• 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.

Multiple Pregnancy

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.

Invasive Procedures in Hepatitis B & C & HIVUse 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

Post Procedure ConsiderationShould 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)

ComplicationFetal 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

Chorionic Villus Sampling

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

Invasive Procedures For Prenatal Diagnosis & Treatment

Mirza Kochak Khan Hospital – 1386-87 1386

1387 CVS 276200مورد

385 مورد254 آمنيوسنتز

38 مورد71 كوردوسنتز

IUT 6645 مورد

Chorionic Villus Sampling

A 18-20 gauge spinal needl

Advantage:

Diagnosis in first trimester & rapid diagnosis

Termination in pregnancy easier and saferPregnancy less obvious, more privateMay be less bondingOne major different with Amniocentesis

is AFP for NTD

• Fetal loss no greater than amniocentesis in experience hand

• Ambiguous results/maternal cell contamination ~1-2%

• Culture failure 1-2%• Placental mosaicism ~ 1%

CVS - Complications

• Experience of operator• Number of attempts• Manipulation required• Route of CVS(TA-CVS

preferable)

Who Report 1991

Factors Affecting Rate ofFetal Loss Following CVS

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

AMNIOCENTESIS

AMNIOCENTESISFirst 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

IndicationChoromosal analysis

DNA diagnosis: single-gen disorder, x-linked disorder

Biochemistry: a-fetoprotein, acetylcholinsterse

Fetal infection

Choroamninitis

Lung maturation

1. Large National Experience2. Lab Techniques Standardized3. Readily Available4. Very Safe5. Very Accurate6. Time to ready answer

Advantages of Mid-Trimester Amniocentesis

AMNIOCENTESISGestational age ( 16-20w) –{Early

amniocentasis}

Comprehensive ultrasound evaluation

Placenta position

Amniotic fluid location

Number of fetus

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

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

Problems AMNIOCENTESIS

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 Obstet Gynecol 1989; 161:382.

Mean amniotic fluid volume during normal pregnancy

12 weeks 14 weeks 16 weeks

40 ml 100 ml 185 ml

PercutaneousUmbilical Cord Blood

Sampling (PUBS)

Fetal Blood Sampling (FBS)

First was report three decades ago

Was first performed under fetoscopic guidance

Use for diagnosis & treatment

Fetal Blood Sampling

Rapid karyotype

Abnormal ultrasound in second & third trimester

Clarify chromosome mosaicism in amniocetesis or CVS

Assess fetal Hb

• Perform from 18w

• 20-22 gauge needle

• Sample site

• Cardiocentesis

Fetal Blood Sampling

Fetal Blood Sampling complication Hemorrhage

Fetal bradycardia ( most common), fetal monitor at least for 30 minate

Intrauterin infection

Fetal loss ~1% ( 0.2%)

Thank you for attention