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.