Of use to O&G and other clinicians

1. KARYOTYPING
Foreword
The obstetric care of a pregnancy, as it is practiced today, includes invasive procedures
for the definitive prenatal diagnosis of fetal disorders correlations dependant on the
results of the chromosomal analysis made upon fetal cells. Sex chromosome trisomies
(SCT), an extra X chromosome in females
(triple X, XXX), males with an extra X
chromosome (Klinefelter syndrome, XXY)
or an extra Y chromosome (XYY) occur
because of errors during meiosis and are
relatively frequent in humans. Their
identification has never been the goal of
prenatal diagnosis (PD) but they almost
escape detection. Testing for serious
genetic abnormalities is more likely to
uncover these trisomies. The indications
to perform prenatal cytogenetic diagnosis
for numerical chromosomal abnormalities
include: abnormal results of prenatal double or triple test, advanced maternal age, fetal
abnormality detected through ultrasound examination, and positive family history for
chromosomal anomalies. Only such an intervention will permit answers to the dilemma
of whether to terminate the pregnancy or to carry it to term.
Dr. Prakash Trivedi
MD [O&G], IVF specialist, Mumbai
Introduction
At conception 23 chromosomes are passed
from each parent to the embryo. The correct
number
of
chromosomes
that
the
cells/embryos should have is 46. However,
there is a statistical chance that one
chromosome will be missing or that one extra
chromosome is present. When this happens it
is termed fetal aneuploidy. Depending on the
chromosomal
abnormality
fetal
loss,
developmental and speech delays, growth
delays, and sexual characteristics may fail to
develop. Down syndrome is an example
where an extra copy of chromosome 21 is
present.
Background
Trisomy 21 (Down syndrome) is associated with mental retardation, malformation of the
heart, gastrointestinal tract, eyes and ears. The overall risk of having an affected fetus is
one in 1,000 live births. Down syndrome is caused by an extra 21st chromosome and is
characterized by mental retardation and specific physical characteristics. It has long
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2. been accepted that women who are 35 years or
older at the time of delivery should be offered
prenatal diagnosis with amniocentesis or
chorionic villus sampling.
Although the risk for trisomy 21 increases with
maternal age, an estimated 75% of affected
fetuses are born to mothers younger than 35
years. Because of this risk, it is important to
provide pregnant women who are younger than
35 years with noninvasive screening for this
trisomy.
Trisomy 18 (Edwards’ syndrome) occurs
in one in every 6,000 births and is
associated with low birth weight, mental
retardation and cranial, cardiac and
renal malformations. Trisomy 18 is also
caused by extra genetic material (an
extra 18th chromosome). Children with
trisomy 18 have severe mental
retardation and life-threatening birth
defects. Most infants affected with this
trisomy die within the first year of life. All
three analytes (AFP, hCG, and UE3)
help test for Down syndrome and
trisomy 18.
Approach
1. As a routine between 15-22 week of pregnancy;
2. If the the screening test reveals abnormal analyte levels, then an ultrasound is
usually recommended because it can sometimes identify the reason for an abnormal
result such as a misdated pregnancy, twins or a birth defect.
3. Amniocentesis will also be offered to test more accurately for spina bifida, Down
syndrome and trisomy 18;
4. If a birth defect is detected, several options may be available including increased
surveillance of the pregnancy, arrangements for special care needed at delivery, or
discontinuation of the pregnancy.
Result interpretation
However, it has to be borne in mind
that a normal triple maternal
screening test does not mean a baby
has no neural tube defect, Down
syndrome or trisomy 18. This is
because the maternal serum triple
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3. screen does not detect every case of Down syndrome, trisomy 18 or spina bifida. We
estimate that it detects 85% of neural tube defects, 80% of pregnancies with Down
syndrome, and 80% of pregnancies with trisomy 18.
Summary
Summary
Findings from one study has categorically revealed that STDMS [second trimester
double marker] is optimal for the detection of fetal DS [Down’s syndrome] in pregnant
women aged under 35. For individual women, if economic condition permits, [second
trimester triple marker] STTMS is the best choice, while for women aged above 35,
STTMS is the best choice in this regard. Noninvasive alternatives to the triple test have
been identified, but these have not been adopted despite 13 years of development. It is
likely, therefore, that the triple test (or variants thereof) will continue to be used in
routine antenatal care for the foreseeable future.
Reference:
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4. 1. Am J Med Genet A. 2013 Nov;161A(11):2873-9, Counseling parents before prenatal
diagnosis: do we need to say more about the sex chromosome aneuploidies?
Lalatta F, Tint GS.
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