About Pregnancy
Introduction
Pregnancy tests are based on the detection of
elevated levels of human Chorionic Gonadotrophin (hCG) in serum or
urine, which is produced by the developing placenta following
implantation1,2. Urine and serum samples of non-pregnant
females usually contain less than 5 mIU/ml hCG3. After
conception levels of hCG in a normal pregnancy will increase
rapidly with levels reaching between 100,000 - 200,000 mIU/ml at
the end of the first trimester1,2,4,5,6. The appearance
and rapid rise in the level of hCG makes it an excellent marker for
pregnancy.
HCG is a dimeric glycoprotein hormone
consisting of an alpha and beta subunit. The alpha subunit is
common to Follicle Stimulating Hormone (FSH), Luteinising Hormone
(LH), Thyroid Stimulating Hormone (TSH) and hCG. The beta subunit
is specific to each hormone and is responsible for its biological
activity7,8,9. The development of antibodies to the beta
subunit of hCG allows reliable measurement of this hormone with no
cross reactivity with the other glycoprotein hormones.
The Function of hCG During
Pregnancy
Pregnancy begins with fertilisation of the egg
and implantation of the fertilised egg in the lining of the uterus.
Implantation will normally occur during the week following
ovulation. hCG begins to be produced around the time of
implantation8.
A pregnancy will usually only continue after
implantation if menstruation is prevented. Estrogen and
Progesterone are produced by the corpus luteum and prevent
menstruation by maintaining the lining of the uterus. The corpus
luteum itself is maintained by hCG that is produced by the
trophoblast cells of the fertilised ovum.
Levels of hCG are considered to be identical
in both serum and urine10,11. HCG levels increase
rapidly in the first stages of pregnancy and will normally begin to
appear in the blood and subsequently in the urine of the pregnant
woman a week after conception. By the day the period is due hCG
levels of approximately 50 - 250 mIU/ml are
expected1,2,4,5,6. During the first trimester, levels of
hCG should double every 48- 72 hours peaking between 100,000 -
200,000 mIU/ml at the end of the trimester, thereafter levels of
hCG drop dramatically with levels remaining well above the basal
level throughout the pregnancy.
Clearview hCG Combo is
sensitive to 25 mIU/ml hCG in both urine and serum samples.
Why Test for Pregnancy?
During the early stages of pregnancy, the
foetus is extremely susceptible to influences from its external
environment. Medical professionals believe that certain measures
should be taken to ensure the best possible chance of the baby
being healthy at birth.
In a hospital environment testing early for
pregnancy allows the mother to avoid exposure to other hazards such
as x-rays, chemicals and medication.
Some infections are more serious in pregnant
than non-pregnant women because of the risk they may pass across
the placental or amniotic barriers. Some examples of these are
Rubella, Toxoplasmosis, Syphilis, Listeriosis and Cytomegalovirus.
Testing early for pregnancy may allow for the mother to test for
immunity to rubella which can cause severe congenital defects or to
avoid foods that might harbour Listeria monocytogenes that could
cause spontaneous abortion16,17.
Smoking can reduce the level of oxygen and
nutrients reaching the foetus and increase the levels of nicotine
in the blood. This increases the risk of spontaneous abortion,
developing placental complications and giving birth to low weight
babies. Alcohol intake during pregnancy can cause growth defects,
central nervous system impairment and facial deformities in the
foetus as well as increasing the risk of spontaneous
abortion11. Early detection of pregnancy is therefore
useful to avoid putting the foetus at risk by smoking and drinking
alcohol.
Research has shown that the incidence of
neural tube defects such as spina bifida and hydrocephalous can be
greatly reduced by taking folic acid supplements both before and
during pregnancy12. Many countries recommend an intake
of 0.4mg of folic acid per day prior to and during the first stages
of pregnancy18. In addition there are certain foods that
should be avoided during pregnancy. Foods which contain high levels
of vitamin A should be avoided as it has been shown to be
teratogenic14. Excessive intake of vitamin D and
caffeine should also be avoided15. Testing early for
pregnancy can therefore help to plan a healthy balanced diet during
pregnancy.
Environmental causes of foetal malformations
account for approximately 10% of malformations, with less than 1%
related to prescription drug exposure, chemicals or
radiation18.
Elevated hCG levels in non-pregnant
individuals
There are a number of medical conditions other
than pregnancy that cause elevated levels of hCG and these may
cause false positive results with Clearview hCG
Combo.
Gestational trophoblastic diseases can result
in partial or complete hydatiform moles (cystic trophoblast tissue
from a non-viable pregnancy) or choriocarcinomas (proliferation of
trophoblastic tissue in the maternal tissues). Hypersecretion of
hCG is common to all conditions19,20. It is also known
that non-trophoblastic neoplasms can hypersecrete hCG. Braunstein
(1980) reported that immunoreactive hCG is found in the sera of
approximately 20% of cancer patients21. It is important
to remember that trophoblastic disease and non-trophoblastic
neoplasms may produce altered forms of hCG and different
proportions of alpha and beta forms8. Clearview
hCG Combo is a qualitative test for the detection of
intact hCG and is not intended for the diagnosis of these
conditions, although these conditions may give positive
results.
Useful links:
http://www.obgynworld.com/
References
1. Braunstein G.D., Rasor J., Adler D., Danzer
H. & Wade M.E. (1976) Serum human Chorionic Gonadotrophin
levels throughout normal pregnancy. Am. J. Obstet. Gynecol. 126(6),
678-681.
2. Chard T. (1992) Pregnancy test ? a review.
Human Reproduction. 7(5), 701-710.
3. Alfthan H., Hagland C., Dabek J. &
Stenman U.H. (1992) Concentrations of human Chorionogonadotropin,
its b -subunit, and the core fragment of the b -subunit in serum
and urine of men and non-pregnant women. Clin. Chem. 38(10),
1981-1987.
4. Lenton E.A., Neal L.M. & Sulaiman R.
(1982) Plasma concentrations of human Chorionic Gonadptrophin from
the time of implantation until the second week of pregnancy.
Fertil. Steril. 37(6), 773-778.
5. Lau H.L., Lawrence K.W., Linkins S.E. &
Jones G.S. (1978) Early detection of human Chorionic Gonadotrophin
in urine by simple immunoassays. Am. J. Obstet. Gynecol. 132(6),
691-693.
6. Hsu M.I., Kolm P., Leete J., Dong K.W.,
Mausher S. & Oehninger S. (1998) Analysis of implantation in
Assisted Reproduction through Use of Serial hCG Measurements. J.
Assisted Reprod Genetics. 15(8) 496-505.
7. Bahl O.P., Carlsen R.B., Bellisario R.
& Swaminathan N. (1972) Human Chorionic Gonadotropin Amino Acid
Sequence of the Alpha and Beta Subunits. Biochem. Biophys. Res.
Commun. 48, 416-422.
8. Hussa R.O. (1987) The Clinical Marker hCG.
Praeger, New York.
9. Strickland T.W. & Puett D. (1981)
Contribution of Subunits to the Function of Luteinising
Hormone/Human Chorionic Gonadotrophin Recombinants. Endocrinology.
109, 1933-1942.
10. Kent A., Kitau M.J. & Chard T. (1991)
Absence of Diurnal Variation in Urinary Chorionic Gonadotrophin
Excretion At 8-13 Weeks Gestation. B J Obstet. Gynaecol. 98.
1180-1181.
11. Cogswell M.E., Weisberg P. & Spong C.
(2003) Cigarette Smoking, Alcohol use and Adverse Pregnancy
Outcomes: Implications for Micronutrient Supplementation. J. Nutr.
133, 1722S-1731S.
12. Czeizel A.E. (2000) Primary prevention of
neural-tube defects and some other major congenital abnormalities:
recommendations for the appropriate use of folic acid during
pregnancy. Paediatric Drugs. 2(6), 437-49.
13. Egen V. & Hasford J. (2003) Prevention
of neural tube defects: effect of an intervention aimed at
implementing the official recommendations. Soz Praventivmed. 48(1),
24-32.
14. Bendich A. & Langseth L. (1989) Safety
of Vitamin A. Am J Clin Nutr. 49(2), 358-371.
15. Ross M.P. & Brundage S. (2002)
Preconception counselling about nutrition and exercise. J S C Med
Assoc. 98(6), 260-3.
16. Grangeot-Keros L. (1992) Rubella and
Pregnancy. Pathol Biol. 40(7), 706-710.
17. Gilbert G.L. (2002) Infections in Pregnant
Women. 175(5), 229-236.
18. Brent R.L. & Beckman D.A. (1994) The
contribution of environmental teratogens to embryonic and fetal
loss. Clin Obstet. Gynecol. 37(3), 646-670.
19. Dreyfus M., Tissier I. & Phillippe E.
(2000) Gestational Trophoblastic Diseases. Classification,
Epidemiology and Genetic Data. J. Gynecol. Obstet. Biol. Reprod.
29(7), 687-689.
20. Quinonez Zarza C. (1995) Hydatiform Mole.
Clinical aspects, incidence and risk factors. Ginecol. Obstet. Mex.
63, 391-394.
21. Braunstein G.D., Rasor J. & Wade M.E.
(1980) Presence of an hCG-like substance in non-pregnant humans.
In: Chorionic gonadotropin. Segal S.J. (ed) Plenum Press, New York,
383-409.