9.3.1 Effectiveness of testsOffering the genetic screening test to all women in the first trimester — regardless of maternal age — is recommended in the United Kingdom (NICE 2008), the United States (ACOG 2007) and Australia (HGSA & RANZCOG 2007).
Summary of the evidenceThe combined test identifies factors that are known to be associated with fetal chromosomal abnormalities and that are independent of each other.
The risk of an adverse outcome (which includes chromosomal and other abnormalities and fetal and postnatal death) increases with nuchal translucency thickness from approximately 5% for a measurement between 2.0–3.0 mm (the 95th percentile) and 3.4 mm to 30% for a measurement of 3.5–4.4 mm, 50% for a measurement of 4.5–5.4 mm and 80% for a measurement of >5.5 mm (Souka et al 1998; 2001).
Combining nuchal translucency assessment with testing of maternal serum increases the predictive value (Alexioy et al 2009). There is strong evidence on the sensitivity of the combined test. For example:
- a good-quality cohort study (n=75,821) (Nicolaides et al 2005) showed the test to have a detection rate of 92.6% at a false positive rate of 5.2% for the detection of trisomy 21 and a slightly lower detection rate for trisomy 18 or 13 and other chromosomal abnormalities;
- another study (n=5,084) (Stenhouse et al 2004) observed a detection rate for trisomy 21 of 93% at a false-positive rate of 5.9% and a detection rate of 96% and overall false-positive rate of 6.3% for all chromosomal abnormalities; and
- a multicentre study (n=8,514) (Wapner et al 2003) found a detection rate of 85.2% for trisomy 21 at a false positive rate of 9.4% and 78.7% at a false-positive rate of 5% and a detection rate for trisomy 18 of 90.9% at a 2% false positive rate.
As fetal nuchal translucency thickness increases with crown-rump length (Pandya et al 1995; Edwards et al 2003) and the detection rate in serum is inluenced by maternal age (Grati et al 2010), these factors are included in risk assessment algorithms. The inclusion of age in risk calculation, either alone or in combination with serum test results, increases detection of chromosomal abnormalities (Wapner et al 2003; Scott et al 2004; Centini et al 2005; Soergel et al 2006; Gebb & Dar 2009; Hagen et a 2010; Schmidt et al 2010). Other relevant factors include maternal weight and height, whether the woman has insulin-dependent diabetes and whether there is a previous history of chromosomal abnormalities (NSW Health 2007).
Offering the combined ultrasound and biochemistry tests reduces the number of women offered diagnostic testing (Saltvedt et al 2005; Marsk et al 2006; Philipson et al 2008; Zournatzi et al 2008; Nadel & Likhite 2009; Lo et al 2010) although some women still opt to have diagnostic testing following a negative screening result (Caughey et al 2007; Hagen et al 2010) and others choose to go directly to the diagnostic test. The combined test may lead to fewer losses of normal pregnancies (Chasen et al 2004) and is cost-effective (Chou et al 2009).
Recommendation - Grade B21. If a woman chooses to have the combined test (nuchal translucency thickness, free beta-human chorionic gonadotrophin, pregnancy-associated plasma protein-A), make arrangements so that blood for biochemical analysis is collected between 9 weeks to 13 weeks 6 days and ultrasound assessment takes place between 11 weeks 0 days and 13 weeks 6 days.
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9.3.2 Supporting women who receive a high-risk result
Referral of women with high-risk resultsFollowing a high-risk result, women should be offered urgent referral to a health professional (eg a genetic counsellor) to discuss their options (see below). In the event that the woman has a diagnostic test and positive result, follow-up with an appropriate health professional should occur at the earliest opportunity. Appropriate heath professionals include experienced midwives, obstetricians, genetic counsellors and clinical geneticists.
Practice pointv. For women with a risk of 1 in 300 or greater, referral to a genetic counsellor should be considered.
Discussing diagnostic testing with womenThe suitability of diagnostic tests is determined by the gestation of pregnancy. The tests are invasive and increase the risk of miscarriage by approximately 1% over and above the background risk of miscarriage from natural causes (NSW Health 2007). Diagnostic tests are based on chromosomal analysis of cells collected using:
- chorionic villus sampling (tissue from the villi of the chorion [part of the placenta]) — testing takes place any time after 11 weeks pregnancy; or
- amniocentesis (to sample fetal skin cells in the amniotic fluid) — testing takes place after 15 weeks pregnancy.
- the chromosomal abnormalities that may be diagnosed;
- the available tests, the gestation of pregnancy at which they should be undertaken, the process of the procedure and the risks involved;
- the possibility that the procedure may not be successful or the result may not accurately reflect the fetal status;
- the possibility of other fetal abnormalities that are not identified by the test;
- the timeframe for receiving results and making further decisions if necessary;
- options to consider if a chromosomal abnormality is identified (eg continuation of the pregnancy or termination where this is permitted under jurisdictional legislation) and the need for additional care if the pregnancy continues (eg specialist management of the pregnancy and the baby);
- long-term implications for the woman and her family of having an affected baby and the health and development issues for children with the condition;
- the impact on a woman and her family of a false negative or false positive result (eg anxiety among women receiving false positives may remain [Green et al 2004]); and
- costs involved and how they are to be met.
Timing of diagnostic testsThere is good quality evidence from a Cochrane review (Alfirevic et al 2003) and a randomised trial (n=3,775) (Philip et al 2004) that amniocentesis before 15 weeks pregnancy increases the risk of miscarriage and procedure-related indicated terminations and the incidence of talipes equinovarus compared to chorionic villus sampling at that time. Transabdominal chorionic villus sampling is the method of choice for diagnosis of fetal chromosomal abnormalities before 14 weeks pregnancy (Philip et al 2004).
Some women may not have the option of chorionic villus sampling (eg if it is not feasible for the test to be conducted before 14 weeks pregnancy or due to placental positioning) and others may choose to wait for amniocentesis after 15 weeks gestation.
Recommendation - Grade B22. If a woman chooses to have a diagnostic test for chromosomal abnormalities, base the choice of test on the gestation of pregnancy and the woman’s preferences. Chorionic villus sampling is safer before 14 weeks pregnancy. Amniocentesis is safe after 15 weeks.
Discussing diagnostic test resultsCareful consideration should be given to the way diagnostic test results are conveyed and experienced interpreters should be used when this is necessary to enable effective communication. Women receiving an abnormal result may be unable to absorb any information for some time and follow-up support may require several consultations. Counselling should be sensitive to the nature of decisions to be taken, should respect individual decisions and allow time to reach decisions (NSW Health 2007). Appropriate follow-up when an abnormality is detected may require referral to genetic counselling services, other professional services or support networks (see Section 9.5).
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If a woman has a normal diagnostic test result, she should be advised of her residual risk as the diagnostic tests have a sensitivity of less than 100%.