Search for in
Antenatal diagnosis of congenital abnormality
Table of Contents
  • Indications for Investigation
  • Blood Tests
  • Genetic Testing
  • Choroid Plexus Cysts (case history)

    • Indications for Investigation

    Congenital abnormalities occur at a rate of 2%, with major defects occurring in 1% of live births. Many genetic and other disorders can now be diagnosed early enough in pregnancy to allow therapeutic options, including termination. The current indications for investigation can be categorised:

    Risk of chromosomal disorder

    • Maternal age >35 years
    • Previous child with disorder, eg. Trisomy 21 (Down's syndrome)
    • Abnormal parent, eg. carrier of balanced translocation
    • Consanguinity (offspring of first cousins risk up to 6%)
    • Risk of gene defects (high risk of recurrence - up to 50%)
    • Metabolic disorders
    • Structural/constitutional disorders, eg. Haemoglobinopathies

    Risk of neural tube defect (NTD)

    • Previous child with NTD
    • Family history of NTD, especially. mother with NTD
    • Diabetes during pregnancy

    Risk of multiple defects

    • Drug or chemical exposure, eg. anti-convulsants
    • Maternal infections, eg. Rubella, CMV
    • Maternal diseases, especially if poorly controlled, eg. IDDM
    Many abnormalities can be detected at the 17-18 week U/S, but accuracy varies with the quality of the machine and the operator, for example, NTD detection rates vary from 60%-95% (MJA 4/10/93). Because of this, serologic testing for NTD is usually also performed. If the risk of physical anomaly is high, referral to a high resolution scanner, with facilities to proceed to genetic tests if indicated, seems wise.

    Blood Tests

    Maternal Serum Alpha Feto Protein (MSAFP)

    AFP is produced by the yolk sac, and later liver, and enters the amniotic fluid and thence maternal serum via foetal urine. In open NTD and abdominal wall defects AFP diffuses rapidly from exposed fetal tissues, so MSAFP levels are much higher. However, MSAFP is also high in twins, pregnancies complicated by bleeding, and in association with intra-uterine growth retardation. Conversely, a low level is seen in failing pregnancies, and in some chromosomal abnormalities such as Trisomy 21. The maternal age related risk for Trisomy 21, per live birth, is approximately:

    20 yrs 1 in 2000
    30 yrs 1 in 900
    35 yrs 1 in 356
    36 yrs 1 in 240
    38 yrs 1 in 180
    40 yrs 1 in 110
    42 yrs 1 in 70
    44 yrs 1 in 40

    Triple Test (oestriol, beta HCG, MSAFP)

    Approx. 60% of chromosomal abnormal infants can be detected in this way but the big disadvantage is the high false positive rate: one in 20 women less than 35 years will be classified as high risk. If applied as a routine screening test in this low risk group, and if each of these women proceeded to amniocentesis (0.5-1% miscarriage rate) or CVS: chorionic villous sampling (1-2% miscarriage rate), an unacceptable number of normal infants is lost. These miscarriage rates are higher in some centres and if more than one attempt is needed. In 20 year old women, for each baby with Trisomy there would be 100 invasive and anxiety provoking procedures, with two normal babies lost.

    The triple test probably serves better in reducing the number of invasive procedures in women over 35 years by identifying the low risk group. If these women are prepared to exchange the 99% accuracy of genetic testing for detection rates of 90% for Trisomy 21 and 60% overall (NEJM 21/4/94), they may avoid the risks inherent in invasive tests, which is an important consideration for mothers whose age reduces their fertility.

    Gene probes

    Gene probes and genetic marker linkage are now available for a variety of disorders,eg. Cystic Fibrosis, Duchenne and Becker muscular Dystrophy, Fragile X Syndrome,Thalassaemia, Haemophilia, and Huntington's Disease. Given the complexity of human DNA, a routine screening for every abnormality is not available. A couple with past, or family, history of disorder is best referred for genetic counselling as there are a number of support services and information packages available. Ideally such referral is made pre conception. The NSW Genetics Education Program (02)94387324 publishes excellent patient booklets on prenatal diagnosis, and a larger directory of services which may be photocopied in part for the family concerned.

     

    Genetic Testing

    The decision for genetic testing is made not just on maternal age, but also on family or previous obstetric history. For example, a previous infant with trisomy 21 means a risk of a further trisomy infant of 1%, but if the child has maternal type translocation Downs syndrome (usually 14;21) the risk is 10%. Some couples opt for testing because of their occupation, eg. workers with disabled children, or those exposed to hazardous chemicals. If testing is found to be abnormal, referral to SAFDA (Support After Fetal Diagnosis of Abnomality) is invaluable.

    Chorionic Villous Sampling

    CVS is performed at 9-12 weeks, and ideally at 10 weeks, to obtain a small amount of chorionic (placental) tissue which is cultured in two to three weeks and can be given recombinant DNA testing. The foetus is too small for U/S diagnosis of morphology and a repeat scan will be needed for this. Equivocal, false (contaminated by maternal genetic material) or non-viable cell cultures occur in 1% and follow-up tests may be required. The main advantage of CVS is the ease with which terminations can be performed if desired, at a time when the pregnancy is able to be concealed from others still.

    Amniocentesis

    Amniocentesis is usually performed at 17-18 weeks. Slightly more accurate than CVS genetically (99.5% vs 98.5%) it allows less time for legal termination (under 20weeks in NSW). Liquor rich in shed fetal cells is cultured, and late in pregnancy may even be tested for fetal lung maturity.

    Cordocentesis

    This involves percutaneous, U/S guided, cord blood sampling for assessment of fetal blood disorders, Rh iso-immunisation haemolysis, fetal infections, and urgent chromosomal karyotyping.

    Rh negative mothers are given anti-D for all invasive procedures.

    Choroid Plexus Cysts (case history)

    Choroid plexus cysts were first described on second trimester ultrasound by Chaudleigh et al in 1984, and reports since then have suggested a link to aneuploidy, esp. trisomy 18 and 21. When I did my training it was commonly held that the cysts themselves were a normal development varient, and would disappear by 23w, but that if they were noted to be bilateral and greater than 10mm the risk of associated trisomy 18 was 5% and trisomy 21 was 1%. Therefore all of these women warranted amniocentesis.

    The trouble, of course, is that ultrasounds are now performed fairly routinely between 16 and 20 weeks in all pregnancies, and the quality of the scanned image is so good , that choroid plexus cysts are popping up in reports all over the place. Reports worldwide currently range from 1 to 3 % of all second trimester scans.

    The current consensus from world literature is that if the scan is otherwise normal in every respect, and if the mother is <35 yrs, the risk of aneuploidy is 1:300, and no further investigation is required. The cysts will spontaneously resolve.

    If, on the other hand, the cysts are noted in combination with one other marker (rockerbottom feet, crossed index fingers, cardiac anomalies, omphalocoele, diaphragmatic herrnia, polyhydramnios, renal anomalies), and if the mother is >35 yrs, the risk of aneuploidy is 1:10.

     

    Sue Page is a general practioner obstetrician in Lennox Head, NSW, Australia.

    This page was last built on 10/01/03. It was originally posted on 12/4/98; 8:40:27 AM.

     Previous Index 1
    Buprenorphine – the 'new’ drug addiction treatment
    		Women's Health
    Index    		 Next
    Amniotic fluid embolism
    © 2007 Northern Rivers General Practice Network
    16 Carrington Street (PO Box 519), Lismore, NSW 2480, Australia.
    Ph: +61 (0)2 6622 4453 Fax: +61 (0)2 6622 3185
    Email: Webmaster Email: Feedback
    Disclaimer and Privacy Statement