Maternal Screening – Part 1 – Maternal Triple or Quadruple screening for Genetic abnormality

Sample

1. These tests are done on the serum of the patient.
2. A urine sample may also be needed.
   1. These tests are done during 14th to 20th weeks of gestation.
3. Supplement these tests by ultrasound.
   1. Ultrasound helps to establish the exact age of the fetus.
4. For confirmation:
   1. Chorionic villus samples may be taken in early pregnancy.
   2. Amniocentesis may be done if needed in mid-pregnancy.
5. First-trimester screening relieves the anxiety of a mother earlier than doing the test in the 2nd trimester.

Precautions

1. The tripple screening test should be done between 15 to 20 weeks of gestation.
2. 16 to 18 weeks are a more accurate test.
3. These screening tests are just warning for fetal abnormality and these are not confirmatory.

Purpose of the test (Indications)

1. These tests diagnose  early pregnancy:
   1. A potential birth defect like neural tube defects or abdominal wall defect.
   2. Chromosomal or genetic abnormalities.
2. These are indicated in women over the age of 35 years.
3. These are also indicated in women who have previous abnormal infants with birth defects.
4. To diagnose trisomy 21 (Down’s syndrome).
5. To diagnose trisomy 18.

Pathophysiology

1. AFP protein is produced by the fetus.
   1. HCG is the hormone produced from the placenta.
   2. Estriol is an estrogen hormone produced by the fetus and the placenta.
2. With the help of these tests can diagnose:
   1. Neural tube defect like myelomeningocele or spina bifida.
   2. Abdominal wall defects like omphalocele or gastroschisis.
3. The incidence of fetal abnormalities is related to the age of women.
4. Down’s Syndrome chances increase with increasing age are:
   1. At the age of 25 years = 1:1300.
   2. At the age of 35 years = 1: 365.
   3. At the age of 45 years = 1:30.
5. In the USA now this screening is offered to pregnant women in the second trimester of pregnancy.
6. The screening tests are not diagnostic.
   1. In case of abnormality in screening tests then confirmatory tests are advised.

Confirmatory tests are:

1. Chorionic villus sampling in the first trimester.
2. Amniocentesis in the mid-pregnancy.

• In the USA mostly women are over the age of 35 years have chorionic villus sampling or amniocentesis.

Screening tests available are:

1. Double screening test. This consists of two markers:
   1. HCG.
   2. AFP
2. Triple screening test. This consists of three markers:
   1. HCG (produced by the placenta).
   2. AFP (produced by the yolk sac and liver).
   3. Estriol (produced by the placenta).
3. Quadruple screening test. This consists of four markers.
   1. HCG.
   2. AFP.
   3. Estriol.
   4. Inhibin A.

4. Triple screening is more popular because it can diagnose trisomy 21(Down’s syndrome) in 50% to 80% of the cases.
5. AFP if done alone will detect only 30% of the case with trisomy 21.
6. Detecting earlier the abnormality,  prepare the family for the coming abnormal baby or they can make the decision to terminate the pregnancy.

Inhibin A

1. This is normally secreted by the granulosa cells of the ovary and inhibits FSH production from the pituitary gland.
2. It is a glycoprotein of placental origin in pregnancy like HCG.
3. It is important in the control of fetal growth.
4. Its level is 2 times higher in trisomy 21 as compared to the normal pregnancy.
5. Its level is lower in normal pregnancy as compared to women with spontaneous abortion.

Pregnancy-associated plasma protein-A (PAPP-A):

1. This is produced by the placenta and the endometrium.
2. Women with low PAPP-A at 8 to 14 weeks has the chances for:
   1. Intrauterine growth restriction.
   2. Trisomy 21.
   3. Premature labor.
   4. Pre-eclampsia.
   5. Stillbirth.
3. In trisomy 21 level is half of the normal level.
4. Low level in the third trimester is associated with severe fetal abnormalities, fetal death, and intrauterine growth restriction.

A positive screening test is seen in:

1. Trisomy 18.
2. Trisomy 21.
3. Neural tube defect.
4. Abdominal wall defects.

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