Genetic counselling

It is good practice to offer genetic counselling before and after diagnostic testing. Such counselling should inform parents and families about the conditions being tested for, and the implications for possible treatments and the continuation of the pregnancy.^[3]

It is important to stress the importance of genetic counselling where possible before pregnancy when there is a family history of any condition which might in pregnancy be tested for by either amniocentesis or chorionic villus sampling (CVS). It is clearly important where possible to avoid unnecessary invasive testing in pregnancy and also to accurately identify where possible specific causes so that appropriate and specific antenatal testing can then be offered.

Indications for amniocentesis

Guidance from the National Institute for Health and Clinical Excellence gives some perspective to the place of amniocentesis in antenatal care.^[4] It is important to highlight that the list of indications will in practice be much shorter with better genetic counselling and the need for earlier diagnosis which often makes CVS a better option.

• Advanced maternal age (>35 years) - the most common indication
• Previous child with:
  • Neural tube defect (1 in 20 subsequent pregnancies affected)
  • Chromosomal abnormalities
  • A birth defect
• Positive antenatal screening tests, including for example:
  • Fetal ultrasound findings^[3]
  • Raised maternal serum alpha-fetoprotein (ultrasound now also used in neural tube defect screening)^[5]
• History of:
  • Parent carrying a balanced chromosomal translocation (1 in 4–10 chance of a fetus being affected)
  • Risk of recessively inherited metabolic disorder
  • Mother carrying X-linked disorder (to determine fetal sex)
  • Mother exposed to certain drugs or infections (which can cause fetal malformations)
• Analysis to detect specific conditions from:
  • DNA (for example, fragile X syndrome, sickle cell disease, cystic fibrosis)
  • Enzymatic activity in amniocytes (for example, Tay-Sachs disease)
  • Fluid biochemistry (for example, in congenital adrenal hyperplasia - 17-OH-progesterone)

Note that testing for lung maturity is relevant only much later in pregnancy rather than in antenatal screening.

Procedure

• Technique:
  • Rhesus immunoprophylaxis should be given where appropriate (fetomaternal transfusion is a risk in amniocentesis and chorionic villus sampling)
  • Preferably under ultrasound guidance
  • 22G spinal needle is inserted through the maternal abdominal and uterine walls into the pocket of amniotic fluid within the amniotic sac
  • 10–20 ml of fluid is aspirated (or approximately 1 ml per week of gestation)
  • A cell filtration system may be used
  • Smaller volumes may be aspirated where advanced laboratory techniques require less material
• Midtrimester amniocentesis:
  • Normally performed in the second trimester from 14–16 weeks' gestation
  • There is relatively more amniotic fluid (enough amniotic fluid for reliable cell culture - about 20 mls)
  • There is still time to terminate the pregnancy (if results indicate this to be advisable)
• Early amniocentesis:
  • This has been conducted at weeks 9–14
  • Less fluid is removed and ultrasound guidance is essential
  • Carries a higher risk of loss of pregnancy (around 7%) and talipes equinovarus^[6][7][8]
  • Preferred over chorionic villus sampling (CVS) where CVS unreliable (in twin pregnancies)

Diagnostic testing of amniotic fluid

It is useful to know what is offered locally as there is some variation across the country. The following tests can be performed:

• On the amniotic fluid:
  • Alpha-fetoprotein (AFP) and acetylcholinesterase levels (for neural tube defects)
  • Bilirubin levels (for gestational assessment and to detect isoimmune haemolysis)
  • Tests of lung maturity (various but lecithin to sphingomyelin ratio for example)
  • Enzyme analysis (many and varied including for inborn errors of metabolism)
• On fetal cells extracted from amniotic fluid testing for genetic and chromosomal disorders:
  • Rapid testing (results in 24 to 72 hours). In most areas this will identify specifically:
    • Down's syndrome (trisomy 21)
    • Edward's syndrome (trisomy 18)
    • Patau's syndrome (trisomy 13)
    • Turner's syndrome
    • Klinefelter's syndrome
    • Other sex chromosome anomalies (in some laboratories, not all)
  • Chromosome analysis after cell culture (results take about 2 weeks). This will give full karyotyping but even this will not identify all chromosomal abnormalities.
• Other possible tests on fetal cells (hardly used in practice with appropriate genetic counselling)
  • Direct DNA analysis techniques (for example for Tay-Sachs disease, phenylketonuria, Duchenne muscular dystrophy and cystic fibrosis)
  • Indirect DNA analysis (used for example to detect linkage disorders when the exact gene is not known)

Patients should be advised of how and when results of testing will be available and this may vary according to the tests being done and the laboratory used.

Risks and complications of amniocentesis

• Distressing symptoms (uterine cramping)
• Uterine bleeding (about 2%)
• Amniotic fluid leakage (about 3%)^[9]
• There is a risk of maternal rhesus sensitisation in susceptible pregnancies (true for CVS as well)
• Amnionitis (only about 0.1%)
• 0.5 - 1% increased risk of pregnancy loss compared with the background risk^[7]
• Failure of cell culture from 1% up to 5% if performed under 12 weeks' gestation
• Anxiety for parents, caused by delay in diagnosis (may make choices for termination of pregnancy difficult)

Other diagnostic techniques

• CVS:^[10] see separate Chorionic Villus Sampling article.
  • Provides diagnosis in the same first trimester period as early amniocentesis
  • Is the technique of choice for prenatal diagnosis before 12 weeks of, for example:
    • Chromosomal abnormalities
    • Genetic disorders (DNA diagnosis)
    • Enzymatic defects (for example, congenital adrenal hyperplasia, lysosomal enzyme defects)
  • Rapid results
  • Lesser risk of pregnancy loss compared with early amniocentesis (~5%)
  • Greater risk of pregnancy loss than midtrimester amniocentesis^[7]
  • More fetal defects (limb reduction, oromandibular defects) especially if performed before 10 weeks' gestation
  • However, it is more technically demanding and not always available^[7][11]

Any benefits of earlier diagnosis with CVS must be carefully balanced against the greater risk of pregnancy loss compared with second trimester amniocentesis.^[12] There appears in some series to be no significant difference in long-term health outcomes between children who had transcervical CVS or amniocentesis for prenatal testing.^[13]