Genomics in general practice

Prenatal testing

Last revised: 30 Nov 2018

Practice point

All pregnant women (ie regardless of age, ethnicity, family history) should be provided with information about prenatal screening tests for chromosomal conditions such as Down syndrome. Screening options should be discussed in the first trimester whenever possible.1,2

Prenatal screening tests should not be considered routine, but offered as a choice to women. General practitioners (GPs) should support women and couples to make informed, independent decisions about the utility of prenatal testing and reproductive options. Women who receive a high-risk screening result should be offered information about diagnostic testing.2

Those identified with a family history of inherited disorders should be made aware of the availability of carrier screening for recessive conditions.1

Pre-pregnancy and pregnancy counselling that are relevant to genetics should include:1,2

  • Any known genetic conditions among close family members (refer to ‘Family history’).
  • History of intellectual disability (ID), multiple pregnancy loss, stillbirth, children with congenital abnormalities.
  • Consanguinity (‘Is there any chance that a relative of yours might be related to someone in your partner’s family?’).
  • Pre-pregnancy and pregnancy folic acid intake.
  • Information about carrier screening (ideally pre-conception or early in first trimester).

All women should be provided information about prenatal screening for chromosomal conditions.1,2
While chromosomal conditions such as Down syndrome are more common in pregnancies of women who are older (the chance of the baby having such a condition tends to increase with maternal age),3 younger women can also have pregnancies with chromosomal conditions.

Prenatal screening information should include the following:

  • Presenting the various screening options and their timing.
  • An explanation of the meaning of results.
  • A discussion of the potential implications of receiving a positive screening result (ie having to undergo an invasive diagnostic test, thinking about the possibility of having a child with special needs or pregnancy termination).

Other important considerations:

  • Screening tests can determine who is at increased risk of having a baby with a chromosomal condition. Women who choose to undertake screening tests should be informed that they will be offered invasive diagnostic testing if they receive a high-risk screening result. Individuals may choose not to proceed with diagnostic testing for a number of reasons

(eg concern about risk of miscarriage, not wishing to know prior to the birth, termination of pregnancy is not an option).

  • Screening tests are non-invasive, so there is no increased risk of miscarriage from the procedure.
  • Every screening test has a false positive rate: some women will receive an ‘increased risk’ result even though their baby is unaffected.
  • In the majority of pregnancies with an ‘increased risk’ screening result, the baby is unaffected. A common misconception is that screening tests ‘show’ that the baby has Down syndrome.
  • ‘Low-risk’ results do not exclude Down syndrome or other conditions.
  • A second trimester ultrasound may detect some physical problems, but it is not recommended as a screening test for Down syndrome.
  • Neural tube defects and other physical conditions may also be detected with second trimester serum screening.
  • Use of the term ‘risk’ in relation to the probability of a diagnosis of Down syndrome (or other disability) should be avoided when discussing prenatal screening with patients because it implies a negative consequence, and can cause offense. The recommended terminology is ‘chance’ or ‘probability’.

Combined first trimester screening

Combined first trimester screening (CFTS) adds different measures together to provide a risk estimate for Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13).

These measures are as follows:

  • Maternal blood to measure pregnancy-associated plasma protein A (PAPP-A) and free ß-subunit of human chorionic gonadotrophin (ß-hCG). Levels of these proteins vary, but tend to be different in women carrying fetuses with Down syndrome or trisomy 18. Increased free ß-hCG with decreased PAPP-A is suggestive of Down syndrome, while decreased levels of both analytes is suggestive of trisomy 18.
  • A nuchal translucency (NT) screening ultrasound.
  • Maternal age, weight and gestation age.
  • In some cases, an additional measurement called the nasal bone is included (presence or absence of nasal bone on ultrasound).

Approximately 5% of CFTS tests give an increased risk result. This figure varies depending on maternal age. Women with an increased risk result should be offered a diagnostic test. The majority of increased risk results are not due to Down syndrome, and most of these babies will be healthy.

There is a partial Medicare Benefits Schedule (MBS) rebate for the blood test component of CFTS; however, there are out-of-pocket expenses for the ultrasound.7

Second trimester maternal serum screening

Second trimester maternal serum screening uses a blood test in conjunction with maternal age and weight, and gestational age to calculate a risk estimate of the chance a pregnancy is affected by Down syndrome, Edwards syndrome or neural tube defects (eg spina bifida).

Second trimester maternal serum screening is for women presenting late in pregnancy. The optimal time to have this test performed is between 15 and 17 weeks, but it can be performed until 20 weeks.

In some cases, there is no out-of-pocket cost for second trimester screening (ie public patient in a public hospital).

Non-invasive prenatal testing or screening

Non-invasive prenatal testing (NIPT; also called non-invasive prenatal screening [NIPS], cell-free DNA [cfDNA] testing) analyses cell-free fetal deoxyribonucleic acid (DNA) found circulating in maternal blood. Testing is usually available anytime from 10 weeks’ gestation. This test analyses the relative proportion of DNA fragments from different chromosomes. If the proportion of fragments from a specific chromosome is increased, then trisomy is suspected.

NIPT is the most accurate screening test available for detecting Down syndrome. Most available NIPT results will provide a risk estimate for trisomies 21, 18 and 13, and sex chromosome aneuploidies (eg monosomy X). Some also provide information about microdeletion syndromes, fetal sex and other autosomal trisomies.

While the accuracy of NIPT in identifying Down syndrome is very high, the accuracy is not as high for Edwards syndrome and Patau syndrome. The accuracy of NIPT is also influenced by the age of the woman and prevalence of the particular condition. For example, the positive predictive value (PPV) will be lower in younger women where the prevalence of chromosome aneuploidies is lower.

NIPT does not screen for:

  • all chromosome aneuploidies
  • single-gene disorders
  • neural tube defects.

It is crucial to perform a 12-week ultrasound alongside, as NIPT is not diagnostic. High-risk results should be confirmed through diagnostic testing. False positive results are possible, and rates vary according to condition.

In some cases, NIPT can be performed as a second-tier screening test before progressing to chorionic villus sampling (CVS) or amniocentesis. Given the higher test sensitivity, a negative NIPT result can reduce the need for CVS or amniocentesis.

Currently, NIPT is not available through the MBS or covered by private health insurance.

The following people should be offered referral to specialist services (genetics or obstetrics):

  • Couples who are known carriers of a genetic condition. Such couples could access Pre-implantation genetic diagnosis through in-vitro fertilisation (IVF) for future pregnancies.
  • Women with an increased probability of a pregnancy with a chromosomal condition
    • previous pregnancy with a chromosomal condition
    • positive screening test or diagnostic test
    • parent with chromosomal rearrangement (eg Balanced translocation).
  • Women with confirmed abnormality from diagnostic testing.

Centre for Genetics Education and The Royal Australian College of General Practitioners, First trimester screening in general practice

Better Health Channel, Pregnancy – Prenatal tests
Centre for Genetics Education, Fact sheet 24: Prenatal testing overview
Centre for Genetics Education, Fact sheet 25: Screening tests during pregnancy
Centre for Genetics Education, Prenatal testing: Special tests for your baby during pregnancy – Includes NIPT

  1. Cardiac Society of Australia and New Zealand. Cardiac genetic investigation of young sudden unexplained death and resuscitated out of hospital cardiac arrest. Sydney: CSANZ, 2011 [Accessed 22 December 2017].
  2. Ingles J, Semsarian C. Sudden cardiac death in the young: A clinical genetic approach. Intern Med J 2007;37(1):32–37. [Accessed 22 December 2017].
  3. Priori SG, Blomström-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Eur Heart J 2015;36(41):2793–867. [Accessed 22 December 2017].
  4. Alders M, Christiaans I. Long QT syndrome. GeneReviews. Seattle, WA: University of Washington, 2003 [Accessed 22 December 2017].
  5. 5. Brugada R, Campuzano O, Sarquella-Brugada G, et al. Brugada syndrome. GeneReviews. Seattle, WA: University of Washington, 2005 [Accessed 22 December 2017].
  6. Cardiac Society of Australia and New Zealand. Guidelines for genetic testing of inherited cardiac disorders. Sydney: CSANZ, 2011 [Accessed 22 December 2017].
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