Prenatal Diagnosis
This usually includes both the screening tests and the diagnostic tests that are available for congenital abnormalities that affect the fetus.Screening tests are performed on all women in order to identify patients who are at high risk of a disorder. They do not confer any risk to the pregnancy and are performed for disorders with a relatively high prevalence and for which there are accurate prenatal diagnostic tests. (Simple, inexpensive & completely safe).
Diagnostic tests are carried out on pregnancies that have been identified as high-risk by a prior screening test. They are usually invasive & carry a small risk of miscarriage.
Screening tests including:
Maternal Hx.
Maternal serum biochemistry.
Maternal virology.
U/S.
Diagnostic tests including:
U/S.
Amniocentesis.
Chorion villus sampling.
Cordocentesis.
Embryoscopy and fetoscopy.
Classification of congenital abnormalities:
1/ Structural, like:
1. Congenital heart disease.
2. Neural tube defects.
3. Cleft –lip /palate.
4. Talipes equinovarus.
2/ Chromosomal, like:
1. Trisomy 21 (Down's syndrome).
2. Monosomy X (Turner's syndrome).
3. Other Trisomies (13,18).
3/ Genetic:
1. Cystic fibrosis.
2. Sickle cell disease.
4/ Miscellaneous: like viral infection.
Screening tests:
History: This is useful for women who have a positive personal or family history of a particular abnormality or syndrome. (such women should be seen at a pre-pregnancy clinic by a medical geneticist for counseling ) .
Maternal age (Screening for Down's syndrome).
Medical history, recent drug therapy, alcohol intake, family history &family history of her partner, the outcome of any previous pregnancy, obstetrical history.
Examination :
* Impaired fetal growth.
* Oligohydramnios.
* Polyhydramnios.
Routine booking test: for .Syphilis. Rubella. Toxoplasmosis. CMV.
Maternal blood tests:
*The presence of fetal cells.
*Alpha – Fetoprotein.
*hCG.
Maternal Serum Alpha-fetoprotein: (MSAFP)
AFP: is a small protein that is produced in large amounts from the yolk sac during the 1st trimester & then from the fetal liver during the 2nd & 3rd trimester. It is a plasma protein that is excreted into the amniotic fluid via fetal urine. It is unknown how AFP crosses the placenta into the maternal circulation. Any condition in which fetal capillaries are exposed to the amniotic fluid will result in elevations of both amniotic fluid AFP & MSAFP.
MSAFP may be high as it leaks out of fetal neurological tissue. (like in neural tube defects.e.g. anencephaly or spina bifida).
Using the MSAFP levels is very dependent upon accurate gestational age.
- Women with raised MSAFP may undergo amniocentesis in order to measure amniotic fluid AFP.
-Women with raised MSAFP & structurally normal fetus are at high risk of preterm labour & small babies & so should be scanned serially.
Causes of high MSAFP levels:
Miscalculated gestational age.Multiple pregnancy.
Threatened abortion.
I.U.D.
Neural tube defects.
Anterior abdominal wall defects ( exomphalos , gastroschisis ).
Congenital nephrosis.
Teratoma.
Miscellaneous anomalies.
Ultrasound examination:
Its use as a screening test in:
1. Recognition of the cranial signs associated with spina bifida (dilated cerebral ventricles and the lemon shape of the skull).
2. Recognition of symmetrically impaired growth, oligohydramnios or polyhydramnios, which should lead to a detailed U/S exam.
3. Recognition of the structural markers of chromosomal anomalies (including cardiac defects, duodenal atresia, omphaloceles, nuchal fat pads &abnormalities of the position of the hands and feet).
Routine U/S:
1st trimester U/S: (early scan)
1) Dating.
2) Fetal anomalies.
3) Determination of chorionicity in multiple pregnancies.
4) Detection of chromosomal abnormalities.
2nd trimester U/S: scanning bet. 18-20 wk.for anomalies.
3rd trimester U/S: to identify abnormalities of the urinary tract or of other organs.
Diagnostic tests:
Apart from U/S these are all invasive procedures, performed with U/S guidance, and carry a risk of losing a normal pregnancy.
Diagnostic U/S:
A very large range of fetal malformations can be identified by U/S imaging. Some may be diagnosed during the 1st trimester by transabdominal or, more especially, by transvaginal scanning. Doppler U/S is also used to study the flow velocity waveforms in fetal circulation (in major chromosomal abnormalities). Colour flow imaging (coloured Doppler U/S) is used to detect cardiac malformation and may assist the diagnosis of renal agenesis (absent renal arteries).
Indications of detailed U/S examination:
1. Decreased fetal movement.
2. The finding of a uterus that is large or small for dates.
3. Polyhydramnios.
4. Oligohydramnios.
5. Palpation of the fetus is difficult.
6. Malpresentation.
7. If a woman who has previously had normally grown babies and now having small fetus.
2. Amniocentesis
It is aspiration of amniotic fluid.
A thin needle is passed transabdominally under U/S guidance into the amniotic cavity (to avoid the placenta &fetus during needle insertion, so the aspiration of amniotic fluid will be without blood contamination). Aspirating about 20ml which contains fetal fibroblasts.
It is performed at or after 15wk.of gestation.
Difficulty occurs when there is :
1. Anteriorly sited placenta.
2. Multiple pregnancy.
3. Maternal obesity.
4. Oligohydramnios.
If the mother is rhesus-negative, she should receive anti-D immunoglobulin
Indications for amniocentesis:
1. Increased maternal age.
2. Hx. of having babies with cong. abnormality or with chromosomal abnormalities.
3. Increased MSAFP or decreased AFP.
4. For lung maturity.
5. For bilirubin level (in Rh-isoimmunization dis.)
Complications: 1. Pregnancy loss (1%).
2. Fetal trauma.
3. Rh-isoimmunization.
4. Leaking liquor → oligohydramnios → lung hypoplasia.
5. S.T. there will be delay in the diagnosis (2-3wk.).
3. Chorion villus sampling (CVS):
It provides earlier & faster karyotypic reports than amniocentesis.
This technique involves sampling trophoblast by inserting a plastic or metal cannula through the cervix, or a needle through the mother's abdomen, under direct U/S guidance.
Transcervical approach may be more suitable in women with low lying posterior placenta and/or a thick abdominal wall.
Transabdominal approach is more safe.
The rapidly dividing trophoblast of early pregnancy obtained by CVS provides suitable tissue for cytogenetic analysis, as well as for DNA & biochemical studies.
The procedure can be performed bet.10-12wk.
Indications: 1) Maternal age >40yr.
2) Both partners being carriers of an autosomal recessive condition (like cystic fibrosis).
3) The need for 1st trimester diagnosis.
Complications:
1) Miscarriages (1%).
2) Limb deformity (if done before 10wk.).
4.Fetal blood sampling (cordocentesis):
Transabdominal needle insertion under U/S guidance provides samples of fetal blood. It is also called cordocentesis or percutaneous umbilical blood sampling, usually targets the umbilical vein at the insertion of the cord into the placenta, although the intra-abdominal umbilical vein, free loop of cord and even the fetal heart have been used.It can be performed bet.20-40wk.of gestation.
Indications:
1) Haemoglobinopathies.2) Fragile X-syndrome.
3) Various infections.
4) Rapid fetal karyotyping. (within 1-3days).
5) Fetal Bl.group, Rh, Hb., Retic.count.
6) Fetal blood gases & PH.
Complications: miscarriages (1%).
Embryoscopy& fetoscopy
It is a small fibreoptic scope which can be threaded through an 18 or even 20 gauge needle.
Advantages:
1) Direct visualization of external features of the skin.
2) Taking a biopsy.
3) Diagnosis of anomalies in the 1st trimester in cases where transvaginal scan is not conclusive. It is possible to introduce a narrow fibreoptic scope through the Chorion and into the extraembryonic coelom to allow visualization of the embryo. (at around 11wk) (embryoscopy).
Screening tests for Down's syndrome
Maternal Hx. & age. ( the risk increases with ↑ maternal age).Maternal biochemistry: by measuring MSAFP ( ↓ ), unconjugated oestriol( ↓ ), hCG ( ↑ ). Down's fetuses appear to behave biochemically as though they are about 2 weeks less mature than their gestational age.
In high risk patients, amniocentesis is recommended.
U/S for nuchal translucency. (abnormal nuchal thickness 2.5mm &more).
Screening tests for trisomy 18:
1. AFP ( ↓ ).2. hCG ( ↓ ).
3. oestriol ( ↓ ).
Screening tests for neural tube defects:
1. MSAFP.2. Amniocentesis (for acetyl-cholinesterase)
3. U/S.
Screening tests for congenital heart defects:
1. Hx.
2. U/S (at 20 weeks).