- New antenatal "reflex DNA" screening for three chromosomal
disorders including Down's syndrome found to be more accurate, safer, and
causing less anxiety to expectant parents
- Current protocol involves initial screening comprising of
ultrasound and blood test followed by an invasive procedure to confirm
diagnosis; this is more stressful to the woman and not as safe as reflex
protocol of antenatal DNA screening of pregnant women for three serious
chromosomal disorders including Down's
is found to be safer, more accurate and one that causes less
tension for the expectant parents according to a recent study by scientists at
the Queen Mary's University London. The findings of the study appear in the
journal Genetics in Medicine.
Diagnosis of Down's Syndrome - New Reflex DNA Testing Protocol
- Currently, pregnant women in the UK
are offered a screening test for three chromosomal disorders including
Down's syndrome at 10-14 weeks gestation.
- The screening test combines an
ultrasound scan and a blood biochemical test.
- After estimation of risk, if these
tests throw up the possibility of the woman having an affected pregnancy
at an estimated risk of 1 in 800 or more, the woman is recalled and
offered a diagnostic test namely amniocentesis or chorionic villus
- Both the above mentioned tests are
invasive and involve insertion of a needle into the womb via the abdominal
wall to obtain samples of the amniotic fluid or placental tissue.
Suggested New Reflex
DNA Testing Protocol
- In the novel protocol followed in
the study, the pregnant woman gave a blood sample around 11 weeks of
- The sample was divided into two parts; one part was used to
perform the conventional
- bloodbiochemical test while
the second part was held in reserve.
- If the estimated risk was found to
be 1 in 800 or more, the reserved
sample was automatically retrieved and a DNA test (reflex DNA testing)
performed to confirm the
Thus the new protocol avoided
informing the patient about the possibility of an abnormal pregnancy causing
undue anxiety and recalling
her for a confirmatory diagnostic test.
Reflex DNA Testing
Protocol - Findings of the Study
The new protocol was implemented in five UK NHS obstetric
units, and more than 22,000 women took part between April 2015 and August 2016;
the protocol still continues to be followed.
The three chromosomal
disorders screened for included Down's syndrome, Edward's syndrome and Patau's
- Out of the 22,812 women screened, 11
percent had reflex DNA testing.
- On reflex DNA testing, it was found
that 101 out of the 106 positive results did have one of the three
disorders. There were only four false positives, which meant 95 percent
accuracy (in comparison to 81 percent with the conventional test alone).
- False positive rate was reduced more
than 100 fold from existing 2.42 percent with the combined test to 0.02
percent with the reflex DNA testing.
- Among the pregnancies that tested
positive, the women were then offered an invasive diagnostic test; 25 out
of 26 women tested were affected by one of these syndromes.
The findings of the study therefore suggest that reflex DNA
testing is superior to conventional
methods presently being followed in terms of safety and accuracy
‘Reflex DNA testing avoids invasive tests like amniocentesis and is safer in addition to being more accurate and less stressful for the expectant mother’
According to Professor Sir Nicholas Wald,
from QMUL's Wolfson Institute of Preventive Medicine, who led the project,
"The reflex DNA approach has substantial benefits to the well-being of the
women screened. Not only are more affected pregnancies identified, but many
fewer women will be made acutely anxious by being notified that they have a
positive screening result, and among those women with a positive DNA screening
result, almost all will have an affected pregnancy. Reflex screening is also
safer than conventional screening as it avoids nearly all invasive diagnostic
tests in unaffected pregnancies and miscarriages related to these procedures".
Other Advantages of
Reflex DNA Testing
Reflex DNA testing also reduces the number
of women who would need counselling as a result of a positive conventional
screening test, and the unnecessary anxiety caused in this group.
Unnecessary invasive diagnostic
procedures such as amniocentesis and chorionic villus sampling are avoided with
potential risks such as miscarriage.
Adds Professor Wald, "The National
Screening Committee is considering a similar proposal, which involves recalling
women with a positive initial result for a DNA test, some of whom will be
sufficiently anxious to request a diagnostic amniocentesis rather than the DNA
test. The reflex method avoids causing
worry to this group, and avoids the dilemma in choosing between a DNA screening
test and a diagnostic amniocentesis
Mr Joseph Aquilina, consultant
obstetrician at Barts Health NHS Trust who participated in the project, said:
"The new reflex DNA approach is transformational. Not only is the
screening method better than current practice, but I have more time to devote to other clinical needs
, as do the
nursing and midwifery staff involved."
- The scientists are also approaching
other hospitals in the UK to check if they would be interested in adopting
the new protocol.
- They claim that reflex DNA testing
could be followed by hospitals worldwide so long as they have access to
labs that can perform the DNA analysis.
If the novel method of reflex DNA testing
does indeed become incorporated in routine antenatal screening program, it
would mean a better overall outcome for the woman which is what modern medicine
aims to achieve.
The normal human cell contains 23 pairs
of chromosomes. Defects in the number or the structure of the chromosomes
result in birth defects and other conditions that may develop during life.
Numerical defects of chromosomes i.e.
presence of an extra chromosome or absence of a chromosome (aneuploidy) is the
most common form of chromosomal abnormality. Down's syndrome (trisomy 21),
Edward's syndrome (trisomy 18) and Patau syndrome (trisomy 13) are all
characterized by the presence of an extra chromosome 21, 18 and 13 respectively
resulting in 47 chromosomes.
Antenatal screening and diagnosis of
these serious disorders gives parents the option to go ahead with or terminate
- Down Syndrome: Prenatal Risk Assessment and Diagnosis - (http://www.aafp.org/afp/2000/0815/p825.html)