antenatal screening

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Antenatal screening and diagnosis are currently available for a few selected genetic conditions, including trisomy 21 (Down syndrome), trisomy 18 (Edward syndrome), trisomy 13 (Patau syndrome) and neural tube defects.

For an overview of the conditions and their manifestations, please refer to the specific articles:

trisomy 21 (general article)
- antenatal features
trisomy 18
trisomy 13
neural tube defects

Screening

The avenues of testing include:

Maternal serum screening

Maternal blood test may be performed during either

1 trimester: as part of the combined serum screening
- performed in conjunction with the nuchal translucency ultrasound (see below)
- performed at 9w-13w6d (ideally 9-12w)
  - the earlier it is performed, the better the detection rate
- measures free βhCG and PAPP-A

or

2 trimester: maternal serum screening (or “quadruple test”)
- performed at 14-20w (ideally 15-17w)
- measures alpha fetoprotein (AFP), free βhCG (or total hCG), unconjugated estriol (uE3) +/- inhibin A

First-trimester ultrasound

First-trimester ultrasound screening involves the measurement of crown rump length (CRL), nuchal translucency (NT) and fetal heart rate. Results are combined with the serum screening to generate a risk.

For screening validity, the test must be performed at 11w3d to 13w6d, or when CRL measures 45-84 mm (if there is a discrepancy, CRL takes precedence).

Nuchal translucency:

<3 mm is considered normal; however, this must be matched with maternal age and gestational age
please refer to the article on nuchal translucency for a discussion of correct measurement
for combined serum screening, a risk of 1 in 300 or less is considered as increased risk

Additional factors that further increase the detection rate and reduce false positive rates include nasal bone, ductus venosus flow and tricuspid flow.

Second-trimester ultrasound

A second-trimester fetal morphology ultrasound scan is generally performed at 18-20 weeks. It is not recommended as the primary screening tool for trisomy 21 or trisomy 18, although it can be used as primary screening for neural tube defects .

Nonetheless, there are a number of structural anomalies that can be diagnosed in the second trimester.

Furthermore, numerous sonographic soft markers may be identified on antenatal ultrasound: features that do not constitute an abnormality in themselves but are associated with an increased risk of congenital anomaly. These are discussed in detail in a separate article.

Non-invasive prenatal testing (NIPT)

NIPT is a recently developed alternative to combined maternal serum screening. It refers to genetic testing done on a maternal blood sample, whereby cell-free fetal DNA is detected in maternal plasma. It is a highly sensitive and specific screening tool (>99% sensitivity and specificity for trisomy 21).

Its availability is currently limited by cost. Furthermore, NIPT screens only for specific chromosomal abnormalities: trisomy 21, 18, and 13, with or without monosomy X (Turner syndrome). Therefore, it should be performed alongside 1 trimester ultrasound for detection of other anomalies.

Initial guidelines recommended NIPT for high-risk women only; however, it is now also available to the general population.

Diagnosis

Diagnostic (as opposed to screening) tests are offered to high-risk patients:

maternal age 37 years or older
increased risk on maternal screening
increased risk on fetal morphology scan

Invasive tests usually offered are

chorionic villus sampling: performed at 11-12 weeks
amniocentesis: performed at 15-18 weeks

Historically, the risk of miscarriage was said to be 1% for CVS and 0.5% for amniocentesis, although this is somewhat operator dependent.

NOTE: This article is currently in accordance with the Australian/New Zealand and UK antenatal screening guidelines. We recognize that some regional variation in the availability and timing of antenatal screening exists.