TRIPLE MATERNAL SCREEN
Maternal serum screening is a valuable tool in prenatal management and is used to
identify pregnancies at increased risk for certain birth defects and chromosomal
abnormalities. Alpha-fetoprotein (AFP) was the earliest serum marker used to detect
open neural tube defects (ONTD) and abdominal wall defects (AWD) respectively) and
with time it was extended to the screening for Down syndrome. Continued
advancements in scientific research resulted in the introduction of a multiple marker
screening panel, or the” triple test” whereby in addition to AFP, the panel included
unconjugated estriol (uE3) and total-human chorionic gonadotropin (t-hCG). According
to the American College of Obstetricians and Gynecologists, it has become standard in
prenatal care to offer screening tests for neural tube defects and genetic abnormalities.
The triple screen is now widely employed in obstetrical practice to detect neural tube
defects, trisomy 18 and Down syndrome (trisomy 21). Counseling patients about the
risks and benefits of such screening is important to provide a balanced discussion of
The recommended screening interval for the triple or quadruple test is between 15 and
22 weeks of pregnancy. Timing
of the prenatal assay and
dating of pregnancy should be
accurate to obtain optimum
Gestational dating may be
obtained by the last menstrual
ultrasound examination is more
reliable in decreasing errors
caused by estimation of
gestational age by the former
The 3 serum analyte figures
vary widely with patients’
demographic status such as
gestational age, number of
fetuses, maternal weight, diabetic status, race and individual history of in vitro
fertilization. Along with serum analyte values, these variables are incorporated into a
mathematical model that calculates a risk value for an individual pregnancy. Levels of
the analytes change with gestational age; the serum value of each analyte is therefore
expressed as MoM (multiples of the median), obtained by dividing the serum analyte
concentration at a particular gestational age by the population median concentration at
the same gestational age. Hence, it is necessary to note that there are many possible
reasons for an abnormal result. It is important to remember that most pregnancies with
an abnormal result are actually normal. Further evaluation of the pregnancy may reveal
an incorrect gestational age, twins, a birth defect or most likely, a normal pregnancy.
The AFP part of the test detects birth defects of
the neural tube, including anencephaly (lack of
development of the fetal skull and brain) and spina
bifida (opening of the fetal spinal column). Babies
with anencephaly cannot survive. Spina bifida can
cause problems ranging from bowel and bladder
control difficulties to paralysis of the legs and
So, as seen above, the levels of the differing
analytes may indicate that the pregnancy has an
increased chance of having spina bifida, Down
syndrome, or trisomy 18. Further tests, such as
ultrasound examination or amniocentesis, may be needed to clarify the test results.
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
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
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 18 th 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.
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.
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
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.
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. ests involving two or more markers in
combination with maternal age are significantly more sensitive than those involving one
marker. The value of combining four or more tests or including inhibin have not been
proven to show statistically significant improvement.
1. American family physician, March 1, 2002, volume 65, number 5, pages 915-920, Maternal serum
triple analyte screening in pregnancy, J. Christopher Graves et al.
2. Biomed Environ Sci. 2013 Feb;26(2):87-93, Validity of different methods to prenatal screening for
Down's syndrom during first and second trimester pregnancy of Chinese-women, Yang F, Wang H,
Shi JC, Hu M.
3. Int J Womens Health. 2010 Aug 9;2:83-8, The triple test as a screening technique for Down
syndrome: reliability and relevance, Reynolds T.
4. Cochrane Database Syst Rev. 2012 Jun 13;6: Second trimester serum tests for Down's Syndrome
screening, Alldred SK.