journal of pediatrics

8/14/2019 Journal of Pediatrics

1/5

Prenatal Screening for Down Syndrome: The Past, Present and Future

ISBN 1015-4361 Journal of Pediatrics, Obstetrics, and Gynecology May/ June 2001

Volume 27 No. 3 page 25-31

SUMMARY

The article traces the development of prenatal screening programmes for Downsyndrome from maternal age to second and then first trimester screening. Future

possibilities for noninvasive diagnosis are also presented.

Down syndrome was first described in 1911 after the observation that a high proportion

of intellectually disabled children in institutions shared common phenotypic features. In

1959, the typical chromosomal appearance of trisomy 21 was described. Down

syndrome remains the most common form of handicap caused by a congenital

abnormality, with high associated mortality and morbidity.

Diagnosis of Down syndrome is made by amniocentesis and chorionic villus sampling

which determines the karyotype of fetal fibroblasts from amniotic fluid and placental

cells.

Extensive research over the last 30 years has lead to the development of a variety of

prenatal tests.

Screening by maternal age

The association of Down syndrome with advanced maternal age has been known

for a long time. The earliest testing programmes generally used a cut-off maternal age

over 40 years. However, as testing became more widespread, it also have been safer

due to improved cytogenic techniques. Australia is an example of the country which

lowered the cut-off age for testing to either 37 or 35 years. The approach leads to a

significant increase in the use of invasive testing, without a large increase in detection

rate. At best, advanced maternal age testing will only detect up to 30% of cases. Due to

the low prevalence of Down syndrome, only one in about 140 women with advanced

maternal age carries an affected fetus.

Second trimester screening

Attempts were simultaneously developed in 1980s whether maternal serum or

ultrasound based screening, to be used in second semester.

Serum based screening

Lower maternal serum alpha fetoprotein, oestriol levels and higher serum of beta

human chorionic gonadotropin levels are the three characteristics of Down

syndrome pregnancies which are used as the basis for the triple test. It was

expected that this would lead to a higher sensitivity and specificity of Down

syndrome, thus improving the detection rate and keeping the invasive testing rate

low. However, almost 10 years after the initial reports of the triple test results

suggest that detection rates of approximately 60% can be achieved with a


2/5

screen positive rate of 5 to 6%. More recently detection rates of 70 to 80% have

been achieved, with a false positive rate of 5%, when maternal age and triple

tests are combined.

Ultrasound-Based Screening

Ultrasound technology introduced in the routine second semester became

apparent that it was possible to recognize some typical features of Down

syndrome which led to the proposal that routine ultrasound could be used as a

screening test. Sonographic features of aneuploidy can be divided into two

groups major or hard signs and minor or soft signs. In these, at least two

soft signs were required before an invasive test was recommended. Also, with

minor defects, it is important to take into account the maternal age-specific risk,

which can be modified by a marker-specific factor to establish the risk for Down

syndrome.

Combined Screening

The combination of the two second trimester screening tests serum screening

results and normal second trimester ultrasound will significantly reduce the

detection rate of serum screening.

First Trimester Screening

Two first trimester markers may be used for screening have been identified with the

help of the rapid advances in ultrasound technology. They are nuchal translucency and

fetal heart rate. Although the role of fetal heart rate still remains controversial and

cannot be recommended.

Ultrasound-Based Screening for Nuchal translucency

Nuchal subcutaneous fluid collections were associated with Down syndrome.

Nuchal translucency refers to the blank space between the nuchal skin and the

atlanto-occipital membrane seen on ultrasound between 11 and 14 weeks. A

study have been done in London which showed that the assessment of risk by a

combination of maternal age and nuchal translucency measurement followed by

selectively termination of all affected fetuses reduces the potential live birth of

incidence of trisomy 21 by about 80%.

Serum-Based Screening

Serum markers of Down syndrome with the move to first trimester screening

measures the combination of maternal age, free -hCG and pregnancy-


3/5

associated plasma protein-A, a detection rate of 68% with a 5% false positive

rate have been reported.

Combined Screening

The serum based screening for the first trimester and the nuchal translucency

measurement has been found to identify 80 to 87% of affected fetuses with afalse-positive rate of 5% in preliminary studies while still allowing immediate post-

test counseling. This screening have been considered by most authorities to be

the most likely recommended screening test of the next few years.

Noninvasive Diagnosis

Noninvasive method of prenatal diagnosis based on isolation of exfoliated

placental cells in the cervical mucus or the isolation on fetal cells found in maternal

circulation are being developed over the last 30 years. The feasibility and reliability of

the first method remains to be established whereas noninvasive attainment of fetal cells

from maternal blood of cytogenetic analysis is already a laboratory reality.

Genetic examination can only be performed on the few collected cells and limited

to fluorescence in situ hybidisation which is for screening of common chromosomal

abnormalities or by polymerase chain reaction techniques which can be used to

determine the absence or presence of specific genetic sequences, however neither of

which provide karyotypic analysis.

Urine-Based Screening

Urinary markers such as -core-hCG, and possibly free -hCG and

oestradiol are another interesting development in futre screening

programmes.

CONCLUSION

With due respect from the authors, I therefore infer the following from the article

Prenatal Screening for Down Syndrome: The Past, Present and Future.

Down syndrome is an abnormality caused by triplication

or translocation of chromosome 21. The abnormalities

include mental retardation, retarded growth, flat

hypoplastic face with short nose, prominent epicanthic

skin folds, small low-set ears with prominent antihelix,

fissured and thickened tongue, laxness of joint ligaments,

pelvic dysplasia, broad hands and feet, stubby fingers,

and transverse palmar crease.

There are prenatal screening programmes for Down syndrome from maternal

age to second and then first trimester screening and some noninvasive

diagnosis.


4/5

Amniocentesis and chorionic villi sampling are the invasive procedure for the

diagnosis of Down syndrome

Advancement of maternal age varies directly with the incidence of Down

syndrome live born infants; as maternal age advances greater incidence of Down

syndrome is observed

Advanced maternal age testing will only detect up to 30% of cases

Second trimester screening includes serum based screening of MSAFP, -

hCG, and oestriol levels; ultrasound based screeningof major and minor signs

in the feature of Down syndrome fetuses; combined screeningwill significantly

reduce the detection rate of serum screening

First trimester screening includes the ultrasound based screening for nuchal

translucency; serum based screening of -hCG and PAPP-A; combined

screeningwhich most authorities now consider to be most likely recommended

screening test of the next few years.

Noninvasive diagnosis have been aimed for the last 30 years extensive research

based on the isolation of exfoliated placental cells in the cervical mucus or the

isolation of fetal cells found in maternal circulation; and by urine-based screening

with the use of urinary markers such as -core-hCG, and possibly free -hCG

and oestradiol in future programmes.

Since fetal cells directly isolated from maternal blood flow do not grow in culture

genetic examination can only be performed on the few collected cells by FISH or

PCR

Consequently, combination of maternal age with second trimester biochemical

screening, and more recently with the measurement of nuchal translucency, have

achieved significant progress in detection rate compared with maternal age

alone.

RECOMMENDATION

Prenatal Screening for Down syndrome recommendations:

I strongly recommend that the option of having the pregnancy terminated after

such screenings be excluded because of the false positive results.

Invasive procedures should be minimized for it may lead to miscarriage and

cause harm to the fetus.


5/5

Maternal age screening should be combined with other screenings in order to

achieve higher percentage of detection.

Urine-based screening must be given greater focus to have new trends in

prenatal screenings of Down syndrome.

I also recommend that researchers, scientists and doctors to not stop in putting

efforts for the betterment of the detection and management of Down syndrome.

Education and notification about Down syndrome should be given a point

especially in public.

Mothers not only those who are in advanced maternal age should also undergo

screenings for earlier detections of other anomalies aside from Down syndrome.

Visual and reading materials should be made for better understanding of the

syndrome.

Health teachings and spiritual guidance must be made available to mothers with

Down syndrome babies.

CHRISTLE ANNE S. UERA

BSN 2Y2 - 7

journal of pediatrics

Documents