Professional Documents
Culture Documents
By Dr. JY Ho (Manipal)
REFERENCES
Hacker & Moore. Essentials of Obstetrics & Gynaecology 5th Edition, 2010. Royal College of Obstetrics & Gynaecology (RCOG) Guidelines. Medscape. Prenatal Diagnosis : Congenital Malformations and Genetic Disorders, 2011. http://www.who.int/whosis/mort/profiles/mort_wpro_mys_ malaysia.pdf. WHO Mortality Country Fact Sheet 2006. American College of Obstetricians and Gynecologists (ACOG). Screening for fetal chromosomal abnormalities. Washington (DC): American College of Obstetricians and Gynecologists (ACOG); 2007 Jan. 11 p. (ACOG practice bulletin; no. 77).
INTRODUCTION
Congenital anomalies account for 20-25% of perinatal deaths worldwide. In Malaysia, congenital anomalies account for 13% of neonatal deaths (WHO Mortality Country Fact Sheet 2006) Prenatal diagnosis employs various non-invasive and invasive techniques to determine the health or any abnormality in an unborn fetus
outcomes of pregnancy Helpful for couples to decide whether to continue pregnancy Indicates possible complications that can arise at birth process Helpful for managing remaining weeks of pregnancy Prepares the couples for the birth of a child with an abnormality Helpful for the improvement of the outcomes of pregnancy using fetal treatment
TECHNIQUES
NON-INVASIVE
INVASIVE
NON-INVASIVE TECHNIQUES
Fetal visualization Ultrasound Fetal echocardiography MRI Radiographs Screening for neural tube defects (NTDs) Maternal serum -fetoprotein (MSAFP) Screening for fetal Down syndrome MSAFP, maternal unconjugated estriol, maternal serum -hCG, serum inhibin A
Separation
blood
Assessment
ULTRASOUND TVS/TAS
Harmless Developing TVS
- accurate dating, fetal location & number, nuchal translucency - cervical length in mid-trimester (identify risk of preterm delivery - placental location in 2nd or 3rd trimester
TAS
- 16-20weeks structural abnormalities - 3rd trimester fetal growth (fetal biometry), amniotic fluid index - biophysical profile (risk of fetal death within a week following BPP score of >8 is less than 1%)
Doppler Guide
invasive sampling
FETAL ECHOCARDIOGRAPHY
Can be performed at 15 weeks gestation & beyond Can identify major structural cardiac defects and rhythm disturbances with duplex or colour flow doppler Recommended when cardiac defects are suspected:
Identification of extracardiac malformations on routine ultrasound y Family history of congenital heart disease y Suspected genetic disease or fetal chromosome abnormality associated with heart defects y Exposure to potentially teratogenic agents
y
SCREENING TESTS
MSAFP Time (Wks) Observation 15-18 Triple Test 15-18 MSAFP &UE3 -hCG Open NTD 65% Downs syn 60% -hCG + PAPP-A 10-14 -hCG PAPP-A Downs syn 65% Nuchal Translucency 11-14 Nuchal thickness 3mm Downs syn 70%
3-5%
5%
5%
5-6%
in Down s syndrome
MSAFP : maternal serum -fetoprotein UE3 : maternal unconjugated estriol -hCG : maternal -human chorionic gonadotropin PAPP-A : pregnancy-associated plasma protein A
Fetal blood cells make access to maternal circulation through placental villi Can be collected at 18 weeks gestation Can be analyzed for the diagnosis of genetic disorders using molecular genetic techniques by isolating DNA and amplifying it by PCR Successfully used in the diagnosis of cystic fibrosis, sickle cell anemia and thalassemia in fetus
INVASIVE
Fetal
TECHNIQUES
visualization - Embryoscopy - Fetoscopy tissue sampling - Amniocentesis - Chorionic villous sampling (CVS) - Cordocentesis (Percutaneous Umbilical Blood Sampling-PUBS) genetic diagnosis (PGD)
Fetal
Preimplantation
Cytogenetic
Molecular genetic techniques Linkage analysis using microsatellite markers Restriction fragment length polymorphisms (RFLPs) Single nucleotide polymorphisms (SNPs) DNA chip Dynamic allele-specific hybridization (DASH)
EMBRYOSCOPY
Performed A
rigid endoscope is inserted via the cervix in the space between amnion and chorion, under sterile conditions & USG guidance to visualize the embryo for diagnosis of congenital malformations
FETOSCOPY
Performed in the 2nd trimester A fine caliber endoscope is inserted into the amniotic cavity through a small maternal abdominal incision, under USG guidance Visualize fetus for structural abnormalities Also used for fetal blood and tissue sampling 3-5% risk of miscarriage
AMNIOCENTESIS
Performed
between 14-20 weeks 22-gauge needle is passed through mothers lower abdomen into clear pocket of amniotic fluid under USG guidance 10-20ml of amniotic fluid obtained 0.5-1.0% fetal loss and maternal Rh isoimmunization (anti-D Ig given to Rh ve mothers) Amniotic cells require 1-2 weeks culture for chromosomal analysis
Genetic
diagnosis - diagnose chromosomal anomalies (trisomy21) - DNA amplification by PCR allow molecular analysis of genetic disorders (cystic fibrosis, sickle cell disease) testing - Amniotic fluid -fetoprotein (AFAFP) - in fetal dorsal / ventral wall defect (NTD, gastrochisis) of perinatal infections - by culture / PCR (CMV,VZV,Parvovirus B19, toxoplasmosis)
Biochemical
Diagnosis
3rd
trimester fetal lung maturity - phosphatidylgycerol, lecithinsphingomyelin ratio amniocentesis - polyhydramnios & twin-twin transfusion syndrome
Therapeutic
CORDOCENTESIS (PUBS)
Features Information obtained
Performed after 16 weeks A 25 gauge needle is inserted into the umbilical cord under USG guidance Fetal blood is collected from umbilical vein for chromosome analysis and genetic diagnosis
Same as in Amniocentesis (but more rapid using fetal leukocyte culture result available in 3 days) Fetal anaemia (superseded by doppler of fetal MCA)
Risk : Fetal loss rate 1% Chorioamnionitis Cord hematoma Thrombosis of umbilical vessels
Women found to have increased risk of aneuploidy should be offered genetic counselling and option of CVS / amniocentesis
Hacker & Moore. Essentials of Obstetrics & Gynaecology 5th Edition, 2010.
* MSAFP detect 80-85% of all open NTDs * Triple screen detect 70% of Down syndrome * Triple screen + Serum Inhibin A detect 81% of Down syndrome
Hacker & Moore. Essentials of Obstetrics & Gynaecology 5th Edition, 2010
Integrated screening - single risk calculation - not reported until after 2nd trimester results are available - highest sensitivity and most most effective Sequential screening - disclosure of 1st trimester results for clinical management
Hacker & Moore. Essentials of Obstetrics & Gynaecology 5th Edition, 2010