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1. Prenatal Diagnostic tests

2. Definition
Pregnancy induces major physiological, hormonal and
biochemical changes to achieve an optimal outcome
for the baby and its mother.
When the pregnancy deviates from its normal course,
there are many biochemical markers which can be
used to assess these abnormalities.

3. Biochemical markers are used to assess maternal, placental
and fetal health. They help to diagnose and monitor
maternal conditions such as gestational diabetes and pre-
eclampsia, trophoblastic disease and fetal chromosomal
abnormalities such as Down's syndrome .
These biochemical and hormonal tests constitute only one
aspect of obstetric care. They should be used together with
clinical findings and imaging, particularly ultrasonography.

4. Some Disorders for which PRENATAL DIAGNOSIS is available:
1. Congenital malformations
2. Chromosomal disorders
3. Non genetic Fetal disorders
4. Single gene disorders
-Multiple malformation syndrome
*Craniosynostosis, Orofacial digital syndrome
-Hematological disorders
*Thalassemias, Hemoglobinopathies, Hemophilia
-Metabolic Disorders
*Tay sach, Wilson,
-Neuromuscular disorders
*Huntington chorea, Myotonic dystrophy

5. Down’s Syndrome
– Down’s syndrome (DS) is a congenital disorder, caused by a trisomy of
chromosome 21
– risk increases with the mother’s age

6. Incidence of Down’s Syndrome
❑ Down syndrome is a chromosomal disorder caused by an error in cell
division, the likelihood of such an error occurring increases with maternal age.
❑This means that an older mother is more likely to give birth to a child with
Down syndrome than her younger counterpart.
❑The likelihood of a woman under 30 years of age giving birth to a child with
Down syndrome is less than 1:1000, but increases the older the woman gets
(see chart below), with an incidence of about 1:100 and 1:30 at 40 and 45
years of age respectively.

7. Neural tube defects
NTD (Neural tube defects) can affect 1 in 500 infants
– Commonest forms of NTD known as anencephaly or spina bifida
– Neural tube beneath the backbone fails to develop definitive diagnosis relies
on amniocentesis
– high levels of AFP (Alphafetoprotein) seen in NTD

8. Gestational diabetes mellitus
(GDM)
Gestational diabetes mellitus (GDM) is a condition in which a
hormone made by the placenta prevents the body from using insulin
effectively. Glucose builds up in the blood instead of being absorbed
by the cells.
Unlike type 1 diabetes, gestational diabetes is not caused by a lack of
insulin, but by other hormones produced during pregnancy that can
make insulin less effective, a condition referred to as insulin
resistance. Gestational diabetic symptoms disappear following
delivery.

9. There are two major problems of gestational
diabetes: macrosomia and hypoglycemia:
•Macrosomia. Macrosomia refers to a baby who is considerably larger
than normal. All of the nutrients the fetus receives come directly
from the mother's blood. If the maternal blood has too much glucose,
the pancreas of the fetus senses the high glucose levels and produces
more insulin in an attempt to use this glucose. The fetus converts the
extra glucose to fat.
•Hypoglycemia. Hypoglycemia refers to low blood sugar in the baby
immediately after delivery. This problem occurs if the mother's blood
sugar levels have been consistently high, causing the fetus to have a
high level of insulin in its circulation. After delivery, the baby
continues to have a high insulin level, but it no longer has the high
level of sugar from its mother, resulting in the newborn's blood sugar
level becoming very low.

10. Pre-eclampsia
Pre-eclampsia is a condition that affects some pregnant women
usually during the second half of pregnancy (from around 20
weeks) or immediately after delivery of their baby.
Women with pre-eclampsia have high blood pressure, fluid
retention (oedema) and protein in the urine (proteinuria).
Although the exact cause of pre-eclampsia is not known, it is
thought to occur when there is a problem with the
placenta. Pregnant women with pre-eclampsia may not realize
they have it.
Pre-eclampsia is usually diagnosed during routine antenatal
appointment. Mild pre-eclampsia can be monitored with blood
pressure and urine tests at regular antenatal appointments and
usually disappears soon after the birth. Severe pre-eclampsia
may need to be monitored in hospital.

11. Condition Test
Maternal Gestational diabetes Glucose screening tests at 24-28
weeks: 50 g challenge test
or
2-hour 75 g oral glucose tolerance test
Pre-eclampsia* 1. Urinary protein (by dipstick testing
or formal quantitation)
2. Serum uric acid
3. Renal function tests
4. Full blood count (for Hb
concentration and platelet count)
Placental Trophoblastic disease* (hydatidiform
mole or choriocarcinoma)
1. HCG
2. Free β-HCG
3. Urinary HCG when indicated
Fetal Down's syndrome* Maternal serum alpha fetoprotein,
HCG, pregnancy-associated plasma
protein-A, and transnuchal ultrasound
between 11 and 13 weeks gestation
Maternal serum alpha fetoprotein,
HCG, pregnancy-associated plasma
protein-A, and serum unconjugated
oestriol in various combinations
between 15 and 18 weeks gestation
Neural tube defects 1. Maternal serum alpha fetoprotein
or
2. Amniotic fluid alpha fetoprotein (less
common)

12. BIOCHEMICAL MARKERS PRENATAL
DIAGNOSIS
1- Alpha-fetoprotein (AFP)
A protein synthesized by the fetus is detectable in maternal serum from
week 6 of pregnancy, with a peak in week 34 of gestation (4 mg / ml), its
value decreasing in 8-12 months after birth.
Measurement of alpha-fetoprotein can be done from amniotic fluid or from
maternal blood.

13. AFP
AFP is a major plasma protein produced by the yolk sac and the fetal
liver during fetal development.
It is thought to be the fetal analog of serum albumin.
AFP binds to copper, nickel, fatty acids and bilirubin and is found in
monomeric, dimeric and trimeric forms.
AFP is a glycoprotein of 591 amino acids and a carbohydrate moiety.
In pregnant women, fetal AFP levels can be monitored in urine. Since
AFP is quickly cleared from the mother's serum via her kidneys,
maternal urine AFP correlates with fetal serum levels, although the
maternal urine level is much lower than the fetal serum level. AFP levels
rise until about week 32.

14. Elevated values of alpha-fetoprotein are found in:
▪Multiple pregnancies
▪Skin diseases;
▪Organ failure;
▪Congenital nephropathy;
▪Hepatic necrosis;
▪Neural tube defects
▪Abdominal wall defects.

15. Low values of alpha-fetoprotein are recorded in cases
1. Chromosomal abnormalities
2. Defects of the placenta
3. Fetal hydrops
4. Trophoblastic disease
5. Diabetic mothers

16. 2-Human Chorionic Gonadotropin
The hormone human chorionic gonadotropin (better known as
HCG) is produced during pregnancy. It is made by cells that
form the placenta, which nourishes the egg after it has been
fertilized and becomes attached to the uterine wall.
Levels can first be detected by a blood test about 11 days after
conception and about 12 - 14 days after conception by a urine
test.
In general the HCG levels will double every 72 hours. The level
will reach its peak in the first 8 – 11 weeks of pregnancy and
then will decline and level off for the remainder of the
pregnancy.

17. There are two common types of HCG tests:
A qualitative HCG test detects if HCG is present in the blood.
A quantitative HCG test (or beta HCG) measures the amount of HCG
actually present in the blood.

18. What can a low HCG level mean?
A low HCG level can mean any number of things and should be
rechecked within 48-72 hours to see how the level is changing. A low
HCG level could indicate
1- Miscalculation of pregnancy dating
2-Possible miscarriage

19. Ectopic pregnancy
An ectopic pregnancy occurs when the
fertilized egg attaches itself in a place
other than inside the uterus. Almost all
ectopic pregnancies occur in a
fallopian tube, and are thus sometimes
called tubal pregnancies. The fallopian
tubes are not designed to hold a
growing embryo; the fertilized egg in a
tubal pregnancy cannot develop
normally and must be treated. An
ectopic pregnancy happens in 1 out of
50 pregnancies

20. How is an ectopic pregnancy diagnosed?
A urine test can show if you are pregnant. To find out if you have an
ectopic pregnancy, your doctor will likely do:
•A pelvic exam to check the size of your uterus and feel for growths or
tenderness in your belly.
•A blood test that checks the level of the pregnancy hormone (hCG).
This test is repeated 2 days later. During early pregnancy, the level of
this hormone doubles every 2 days. Low levels suggest a problem,
such as ectopic pregnancy.
•An ultrasound. This test can show pictures of what is inside your
belly. With ultrasound, a doctor can usually see a pregnancy in the
uterus 6 weeks after your last menstrual period.

21. What can a high HCG level mean?
A high level of HCG can also mean a number of things and should be
rechecked within 48-72 hours to evaluate changes in the level.
Miscalculation of pregnancy dating
Molar pregnancy
A molar pregnancy is an abnormality of the placenta, caused by a
problem when the egg and sperm join together at fertilization. Molar
pregnancies are rare, occurring in 1 out of every 1,000 pregnancies.
Molar pregnancies are also called gestational trophoblastic

23. 3-Unconjugated estriol
Estriol (E3) is one of the three major naturally occurring estrogens,
the others being estradiol (E2) and estrone (E1).
In non-pregnant females, the major estrogen is estradiol produced
by the ovaries.
During pregnancy, estriol is secreted by the placenta and fetus and
becomes the dominant estrogen form.
The primary form of estriol measured during pregnancy is
unconjugated estriol (also referred to as “free” estriol or uE3).
Maternal serum E3 levels have been used as a functional marker of
the fetal-placental unit and in the evaluation of pregnancy
complications.

24. 4- Inhibin - A
Inhibins are glycoprotein hormones of which there are two molecular
forms, inhibin A and inhibin B.
Classically, inhibin is known to have a negative feedback effect on pituitary
follicle-stimulating hormone secretion.
Inhibin A is the predominant molecular form of inhibin in maternal
circulation from 4 weeks of gestation.
The precise biological function of inhibin A in pregnancy is could be a
better marker of placental function than human chorionic gonadotropin
because of its shorter half-life.

25. 5-Pregnancy-associated plasma protein-A
It largest of the pregnancy associated proteins produced by both
the embryo and the placenta during pregnancy
This protein is thought to have several different functions,
including preventing recognition of the fetus by the maternal
immune system, matrix mineralization and angiogenesis.
Detection of this protein is also suggested as a first and second
trimester diagnostic test for aneuploidies, including Trisomies 21
or Down’s Syndrome

26. Fetal tissue sampling techniques
The prenatal diagnosis of
many chromosomal and
genetic abnormalities
requires tissue sampling.
Various techniques are
available