Universal screening and case finding

Screening is the systematic application of a test to identify individ­uals at sufficient risk of a specific disorder to benefit from further investigations. The concept of universal screening for prenatal diag­nosis started in the United Kingdom in the 1980s.

The screening for chromosomal abnormalities started with the introduction of maternal age as a risk factor. Any pregnant woman over 35 years old was offered an invasive test to detect chromosomal defects, in particular trisomy 21 (Down syndrome). This initial ap­proach detected about 50% of trisomy 21 cases with a high false­positive rate (1). In the 1980s, the screening consisted of maternal serum biochemistry and a detailed anomaly scan in the second trimester. The combined first-trimester screening was introduced in the 1990s. It combines maternal age, nuchal translucency (NT), and biochemical markers in maternal serum (beta-human chori­onic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A)). This test increased the detection rate to 90% with a false-positive rate of 5% for trisomy 21 and is the currently recom­mended method for screening in the United Kingdom and most developed countries (2). It was recently discovered that small frag­ments of cell-free fetal DNA are present in maternal blood, and can be used to test for chromosomal abnormalities. The introduction of cell-free fetal DNA testing (also known as non-invasive prenatal testing or NIPT) has improved the detection rates of trisomy 21 to 99%. However, it is still not universally available (3).

Parallel to the screening for chromosomal defects, the intro­duction of a routine anomaly scan in the second trimester (18-21 weeks) was aimed at prenatal identification of major structural abnormalities.

In order to obtain uniformity in the prenatal screening, and to improve the neonatal morbidity and mortality, the National Health Service (NHS) Fetal Anomaly Screening Programme (FASP) (4) guidelines have introduced a series of recommendations:

• Ensure access to a uniform screening programme which conforms to an agreed level of quality.

• Provide appropriate information for women so that they can make an informed choice.

• Offer choices to women about their screening options and preg­nancy management.

• Identify serious fetal abnormalities, either incompatible with life or associated with morbidity, allowing women to make repro­ductive choices.

• Identify abnormalities that may benefit from antenatal intervention.

• Identify abnormalities that require early intervention following delivery.

The lower limit of the gestational age window was selected to ac­knowledge the ability to examine the fetal anatomy thoroughly and competently from 18 completed weeks (i.e. 18⁺⁰ weeks) as a few of the abnormalities could be missed at an earlier gestation. The upper limit of 20⁺⁶ weeks was selected to allow sufficient time for referral to a tertiary centre, subsequent assessment to be undertaken, and, when indicated, termination of pregnancy to be available before the legal limit for pregnancy termination (24 weeks in the United Kingdom). The Standards (Standard 4—Clinical arrangements) also recommend that a woman with a suspected or confirmed fetal anomaly should be seen by an obstetric ultrasound specialist within three working days of the referral being made or by a fetal medicine unit within five working days of the referral being made (4, 5).

There are two approaches with screening—one is to offer ultra­sound to all women (universal screening), and the other is targeted screening to those deemed at high risk. The majority of fetal abnor­malities are encountered in women without risk factors. Therefore, the policy of universal screening is appropriate.

Earlier studies have shown that the sensitivity and specificity of ultrasound in detecting fetal anomalies in a low-risk population are 40% and 85% respectively (6-8). The Routine Antenatal Diagnostic Imaging with Ultrasound Study (RADIUS) concluded that the sen­sitivity was only 35% for major fetal anomalies (9).

It is acknowledged that there are some cohorts deemed at high risk for having an affected fetus:

• Women with type 1 diabetes have a higher risk of congenital heart abnormalities (10).

• Women with epilepsy and on antiepileptic medication have a higher risk of neural tube defects (11).

• Fetuses with an increased NT have an increased risk of various structural abnormalities in addition to chromosomal abnormalities (12).

• Women with a previous fetus affected by a structural abnormality (e.g. spina bifida) (13).

• Women found to have a high serum alpha-fetoprotein are known to be associated with a higher risk of neural tube defects and ab­dominal wall defects.

When ultrasound scanning is performed on an indication basis on these ‘high-risk’ women, the sensitivity is much higher, in the range of 86-99%. But it could be argued that many of the anom­alies occur in low-risk women, so it is reasonable to offer screening universally.