TRIPLE MATERNAL SCREENForewordMaternal 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 screening issues.

IntroductionThe 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 value of each analyte. Gestational dating may be obtained by the last menstrual period, although early ultrasound examination is more reliable in decreasing errors caused by estimation of gestational age by the former method.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.

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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 learning disabilities.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.

BackgroundTrisomy 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 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 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.

Approach1. 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.

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Result interpretationHowever, 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.

Summary

ConclusionFindings 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

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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.

Reference: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.

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