Health Information Library
» Biochemistry Screening for Down's Syndrome
1st Trimester Biochemical Test
Maternal serum free beta-hCG
Free beta-hCG levels decreases with gestation after 10 weeks. In Down’s syndrome affected pregnancy the level is increased. When it is performed alone between 10-14 weeks gestation, and we set the cut off for a 5% screen-positive rate, the detection is about 35%, and in combination with maternal age increased to 45%.
Maternal serum PAPP-A
PAPP-A increases with gestation, but in Down’s babies the level is lower. For a 5% screen-positive rate, PAPP-A detects about 40% of Down’s syndrome babies, and in combination with maternal age, it increases to about 50%.
Maternal serum free beta hCG and PAPP-A
When the two biochemical tests of 1st Trimester are combined with maternal age, the detection rate is estimated to be 60% for a 5% screen-positive rate.
Combined Test
(Nuchal translucency + maternal serum free beta-hCG + PAPP-A)
When the three are combined, together with maternal age, the estimated detection rate is estimated to be 85-89% for a screen-positive rate of 5% (i.e. the top 5% of the screened population was tested). Or to look at it another way, for a 5% false-positive rate (i.e. 5% of patients being tested have a normal baby) the detection rate is 85%.
To look for more information on “2nd trimester biochemical testing” please refer to Second trimester Biochemical Testing.
» Invasive Prenatal Diagnosis
If you feel that your individual risk is high for Down's syndrome – because of your age or the nuchal translucency screening in the first trimester, or biochemical testing in the 1st/2nd trimester, or increased suspicion due to the presence of anomalies or soft markers at the second trimester anomaly scan, further tests can be performed to reach a definitive diagnosis.
In order to reach a definitive diagnosis of chromosomal abnormality, it requires fetal cells to be obtained, cultured and analyzed. This can be obtained either by chorion villus sampling at 11-13 weeks, or amniocentesis from 14 weeks onwards.
Chorion villus sampling at 11-13 weeks
Both the baby and the placenta have developed from the same cell, by examining the placental tissue, we can diagnose chromosomal abnormalities in the fetus.
The procedure is normally performed without the need of local anaesthetic. A needle is passed through the mother’s abdomen under ultrasound guidance and a sample of placental tissue is obtained. The whole procedure only takes a few minutes, and heartbeat is checked at the end of the procedure to ensure that the baby is well.
The sample is cultured, and the cells analyzed. A preliminary report should be available in 12-14 days, with the definitive result in about 3 weeks. Recently, the application of FISH and PCR techniques makes it possible to have a preliminary result within a few days. As soon as we get the result, we shall call and let you know. In about 1% of cases the culture fails to grow or are inconclusive, in which case, the procedure may need to be repeated.
You may experience some abdominal discomfort for the first few days after the procedure and a little bleeding. This is relatively common, and in most cases, there is nothing to worry about. Some painkillers such as paracetamol may be helpful to relieve the pain. Should you experience a lot of pain or heavy bleeding, or develop a high temperature, you should seek medical advice.
There is a miscarriage risk of about 1.4% associated with the procedure, which is slightly higher than for amniocentesis at 16 weeks. Should this happen, it usually happens within 1 week of the procedure.
Amniocentesis after 14 weeks
Fetal cells are present in the amniotic fluid. By culturing and examining the cells obtained, we can diagnose chromosomal abnormalities.
The procedure is normally performed without the need of local anaesthetic. A needle is passed through the uterus and fluid is removed for analysis. The whole procedure only takes a few minutes, and heartbeat is checked at the end of the procedure to ensure that the baby is well.
The sample is cultured, and the cells analyzed. A preliminary report should be available in 12-14 days, with the definitive result in about 3 weeks. The recently established PCR technique enables a quick preliminary result within 3 days. As soon as we get the result, we shall call and let you know. In about 1% of cases the culture fails to grow or are inconclusive, in which case, the procedure may need to be repeated.
You may experience some abdominal discomfort for the first few days after the procedure and a little bleeding. This is relatively common, and in most cases, there is nothing to worry about. Some painkillers such as paracetamol may be helpful to relieve the pain. Should you experience a lot of pain or heavy bleeding, or develop a high temperature, you should seek medical advice.
There is a miscarriage risk of about 0.9% associated with the procedure, which is slightly lower than for chorion villus sampling.
Amniocentesis can be performed earlier, but this appears to be less safe in some studies compared to chorion villus sampling at 11-13 weeks.
» Laboratory tests
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Complete Blood Count (CBC)
Sexually transmitted diseases (VDRL, HIVab, Chlamydia)
Kidney function (urinalysis, urea, creatinine, sodium, chloride, potassium)
Liver function (AST/SGOT, ALT/SGPT, Bilirubin, Alkaline Phosphate, Gamma GT,
total protein, Globulin, Albumin)
Hepatitis B screening (HbsAg, HbsAb)
Diabetes screening (fasting glucose)
Glucose tolerance test
Lipid profile (total cholesterol, HDL, LDL, Triglycerides, Lipo protein pattern)
Thyroid function test (T4, T3, TSH, TBG)
Gout screening (uric acid)
Fertility screening profile (BhCG, Prolactin, LH, FSH, E2, DHEA-S, progesterone)
Full cancer screening profile including AFP, CA15-3, CA19-9, CA125(Tumor marker),
CEA(Tumor Marker), EBV(NPC), BhCG (Trophoblastic), SCG(Cervix, Head, Neck), CA72-4
» Mammography
Breast cancer is the most common cancer in women, and is the number 2 killer in Hong Kong. Recent studies have shown that there is a trend for younger women to be affected.
Because the human breast is made of tissue and fat, very small lumps may not be easily felt. A mammogram (x-ray picture of the breast) can pick up calcification and early malignant changes. This means you have a better chance of surviving the disease as well as more choices as to how to treat it.
Studies have shown that breast screening with mammography reduces the number of deaths from breast cancer for women aged 40 to 69 and is the gold standard in breast screening. You should consider a base line scan at around 35 years old, and then repeating it after 3 years, provided there is no increased risk of breast cancer. After 40 this should be repeated every 2 years. For women who are at increased risk, they should have it repeated every year.
Women who are at increased risk include :
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Personal history of breast cancer – previous breast cancer increases the chances of a second.
Family history – mother, sisters, daughters or >2 close relatives, e.g. aunts, cousins, have a history of cancer, especially if it developed under the age of 50.
Genetic alterations – About 10% of breast cancer patients have some specific alteration in their genetic makeup (e.g. BRCA1 and BRCA2) that renders them much more susceptible to the disease.
Breast changes – women previously diagnosed with atypical hyperplasia or lobular carcinoma in stiu, or having had 2 or more biopsy for benign disease.
Menstrual and obstetric history – 1st child after 30 years of age, 1st period before 12 years old, late menopause after 55 years, never had children, and women on HRT for greater than 5 years.
Radiotherapy – women whose breasts have been exposed to radiotherapy in the past for the treatment of other diseases.
At The Women's Clinic we have installed the specialized X-ray machine called DEDICATED MAMMOGRAPHY, which is designed to have low x-ray emission, with negligible risk.
When you undertake a mammography, the technician will gently squeeze your breasts with a paddle on the machine, and the pressure may be slightly uncomfortable, but the flatter the breast, the clearer the image, and it should not take longer than a few minutes.
The x-ray films will be reviewed by our specialists and the result will be given to your doctor.
» Nuchal Translucency
When Langdon Down first described Down’s syndrome in the 1866, he noted that the babies born with the syndrome appeared to have an excessive amount of skin in relation to the size of the baby.
This relationship was observed in utero in the 1990s, where the fetuses demonstrated an increased amount of fluid at the back of the neck (nuchal translucency) when scanned in the 1st trimester. This has led to the development of screening by ultrasound scan at 11-14 weeks gestation for Down’s syndrome. As the fetus grow, the nuchal translucency also increases, hence it is important to date the pregnancy accurately.
This thickness in combination with maternal age, previous history of chromosomal defects and gestation made it possible to detect about 75% of babies with Down’s syndrome for an invasive testing (that is, chorionic villus sampling or amniocentesis) rate of 5%. As the thickness increases, the risk also increases. The reverse is also true, and by multiplying the ‘test factor’ against the background risk, it is possible to give each woman her unique risk for Down’s syndrome for that particular pregnancy. Armed with this risk, you and your partner can decide whether the risk is sufficiently high for you to have invasive testing performed.
Furthermore, increased nuchal translucency is also associated with other genetic syndromes, chromosomal abnormalities (Trisomy 13, Trisomy 18, triploidy, Turner’s syndrome) and major congenital defects of the cardiovascular system as well as skeletal dysplasia, fetal anemia and infection.
Other biochemical screening is also available and can be performed independently or combined with nuchal translucency to give a higher detection rate. Please see non–invasive screening for Down’s syndrome for further details.
» Osteoporosis
Osteoporosis is caused by the loss of calcium in bone, resulting in a decrease in bone density. A loss of minerals will make the bone brittle and liable to fracture. In general, bone loss is silent until pain or fracture occurs. It is common amongst post-menopausal women particularly between the 5th and 7th years, during which the loss of calcium can reach 20%. The decrease of estrogen level will accelerate the loss of calcium, which leads to the loss of bone tissue and finally fracture and pain. Osteoporosis is a debilitating disease but early diagnosis helps to prevent it. Bone densitometry can help early detection and appropriate treatment.
( A graph to show the correlation between age and bone density )
Who are vulnerable to osteoporosis?
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Women who are menopausal or if the ovaries are removed surgically
Family history of osteoporosis, or having a thin and small-boned habitus
History of very irregular periods, or not having periods for over 6 months
Long term intake of certain drugs, e.g. steroid and thyroid hormone
Lack of exercise and outdoor activities
Chronic insufficient intake of calcium, especially during childhood and
insufficient milk absorption
Smokers and alcoholics
Do I need bone densitometry if I am taking hormonal replacement treatment?
Studies have shown that by keeping the oestrogen (female hormone) at a sufficiently high level, it will prevent/modify osteoporosis formation. Bone densitometry and a concurrent hormone assay are necessary for monitoring the bone mass level.
Which type is your bone like? Normal bone Vs Osteoporotic bone (see right photos)
To look for the nutrient and energy content of various food for calculation of daily diet intake, please take a look at the Table of Food Nutrient and Energy Content.
» Relationship of Bone Mineral Density with Age
The graph below showing the Bone Mineral Density decreases with age
Bone densitometry is proved to be a useful predictor of bone density and hence, the risk of osteoporotic fracture to occur. The bone mineral density increases during the puberty period until the age around 35. It levels off towards menopause especially from the first six to eight years during which 1% to 5% of bone density will be lost.
To see if you are at risk, please go back to Osteoporosis.
Note: * The World Health Organization (WHO) has defined osteopenia the followings for white women [“SD” means Standard Deviation]
- - 1.0 SD = normal;
- - 1.0 to – 2.5 SD = Osteopenia;
- < - 2.5 SD = Osteoporosis
Scanning of AP Spine by the DEXA Bone Densitometer
Scanning Report as below shows the level of the BMD comparing to the reference score
» Second Trimester Anomaly Scan
Between 20-24 weeks gestation, fetal anomaly scanning is usually performed to look for any abnormalities in the fetus. This involves systematically assessing all the major organs in the baby, and if appropriate, its function.
2D ultrasound scanning: foetal profile at 12 weeks
3D ultrasound scanning: 12 weeks foetus looking cross-sectionally through the head
Most chromosomal abnormalities will review multiple anomalies in the baby, and these are known as markers. These markers are well documented, and can be visualized on ultrasound scan.
In the case of Down’s syndrome, it may reveal that the baby has mild dilation of the fluid filled space in the brain, flat features, box like head, heart defects, blocked small bowels or very bright bowels, gap between the toes, shortening of the little finger, shortened limbs and mildly dilated kidneys.
These markers may not be present in all cases, and may even be completely absent; but as the number of defects increases, the risk of Down’s syndrome also increases.
However it is important to stress that these markers are very common, and the baby is usually normal. Routine invasive testing of all pregnancy in the presence of these markers is not always indicated, especially when it isn’t without risk.
Certain of these markers have had their likelihood ratio worked out, for example, isolated very bright bowels increase the risk of Down’s syndrome by 3 times the background risk, and large nuchal fold in the 2nd trimester of > 6mm increases the risk of Down’s syndrome by 15 times.
To define the risk to the individual, they can be combined with first trimester screening and/or biochemical testing, to further modify the individual risk. This is achieved by multiplying the likelihood ratio of individual markers with the background risk, as these are independent variables that are not interrelated to the nuchal translucency and / or biochemical testing. This will give a modified risk for the individual, and you and your partner can decide whether the risk is sufficient for further testing.
A normal 2nd trimester scan is reassuring, and some claims halved the background risk.
To look for information on “Invasive Prenatal Diagnosis” please click here.
» Second Trimester Biochemical Testing
Double Test
This is performed during the second trimester, measuring the maternal serum alpha-fetoprotein and hCG levels. When combined with maternal age, there is a 59% detection rate for Down’s syndrome for a 5% false positive rate.
Triple Test
This test measures the maternal serum alpha-fetalprotein, hCG and estriol levels, and has a 69% detection rate for a 5% false-positive rate.
Integrated test
This combines the 1st trimester serum screening, with nuchal translucency and the second trimester triple test. Together with maternal age, the detection rate for Down’s syndrome is 92% for a 5% false positive rate. When the second trimester double test is used, the detection rate is slightly lowered. When Inhibin A is added to the second trimester serum screening (quadruple test) to form the integrated test, the detection is estimated to increase to 94%.
To look for more information on “2nd trimester anomaly scan”, please click here.
» Semen Analysis
It is usually said that the problems of infertile couple, 40% of the time it is due to male factor, 40% due to female factor, and the remaining 20% due to both. Therefore, it is essential to perform an accurate semen analysis.
At The Women's Clinic we endeavor to perform the most detailed semen analysis according to the latest World Health Organization (WHO 1999) recommendations, using the Hamilton Thorn computerized system, thereby eliminating any observer bias or errors.
According to the WHO all semen samples should have their appearance, volume, liquefaction, viscosity, agglutination, pH, motility, leucocytes count, sperm count, vitality, morphology and anti-sperm antibodies tested.
A normal semen sample should have a white appearance (discoloration may indicate pus cells or presence of blood}, with a volume of greater than 2ml after 2 days abstinence.
On contact with air, semen coagulates after ejaculation, and over a period of time, this liquefies. Liquefaction should be complete within 1 hour after ejaculation. The viscosity at this stage should be of a watery consistency, and the pH no less than 7.2.
Agglutination is defined as motile sperms stuck together, and may indicate the presence of antibodies. Anti-sperm antibodies should also be tested for routinely in all samples, and any levels that are greater than 50% indicates a high probable immunological cause for the infertility.
Motility measures the percentage of moving sperms and is graded into
– Actively progressively motile – Slowly progressively motile – Non progressively motile – Non motile
Normal semen at 1 hour post ejaculation should contain greater than 50% Grade A + B sperms with at least 25% grade A. The vitality of the sample (percentage of sperm that is alive, not necessarily motile) should be more than 50% at this stage.
Pus cells should also be looked for, and if it’s greater than 1 million /ml, it may indicate infection. The sperm count fluctuates enormously even in normal fertile man, they can produce samples that are lower than the minimum of 20 million/ml on occasions, and 2 samples at least should be required for semen analysis.
Normal morphology is defined as greater than 14%, or in other words, up to 86% of abnormal looking sperm still qualifies as within the normal limit. This might appear surprising, as not infrequently some analysis reports a normal morphology of greater than 60%, but these tests are not be based on the recommendation and criteria of the WHO, and should be interpreted with caution.
What should I do if I want to have a semen analysis?
To look for more details please click on » Semen Collection Procedures
"Produce a Semen Sample"
» Table of Food Nutrient and Energy Content
Table of nutrient and energy content of various food for calculation of daily diet intake
| Food item | Protein (g) |
Fat (g) |
Carbohydrate (g) |
Energy (Kcal) |
| 1 slice of toast or bread |
2
|
0
|
20
|
88
|
| 1 bowl of rice |
5
|
0
|
50
|
220
|
| 1 bowl of noodle |
4
|
0
|
40
|
176
|
| 1 no. of potato (egg-sized) |
1
|
0
|
10
|
44
|
| 1 piece of lean pork chop (2 tael or 3 oz) |
21
|
15
|
0
|
219
|
| 1/2 steamed whole fish (2 tael or 3 oz) |
14
|
10
|
0
|
146
|
| 1 drumstick (2 tael or 3 oz) |
16
|
12
|
0
|
172
|
| 1 large block of bean curd |
10
|
0
|
5
|
60
|
| 1 bowl of leafy vegetable (stir-fried) |
2
|
2
|
5
|
46
|
| 1 no.of orange or small apple |
0
|
0
|
20
|
80
|
| 1 glass of milk (250 ml) |
6
|
6
|
20
|
158
|
| 1 glass of skim milk (250 ml) |
6
|
1
|
20
|
113
|
Energy requirements
For weight maintenance:
Man 1800 -2000 Kcal/day
Woman 1500 -1800 Kcal/day
For weight reduction at a rate of 2 Kg/month, with 15-20 minutes of light activity daily:
Man 1500 -1800 Kcal/day
Woman 1200 -1500 Kcal/day
For weight reduction at a rate of 2 Kg/month, with no exercise:
Man 1500 Kcal/day
Woman 1000 -1200 Kcal/day
» Ultrasound Diagnosis in the 1st, 2nd and 3rd Trimester
At Create Health we offer a comprehensive 2D, 3D and 4D (active real-time motion and expression) ultrasound scanning to all pregnant women, using the latest cutting edge technology. The vast majority of ultrasound scans are done through the abdomen – although in early pregnancy and when examining the cervix and low lying placenta at any stage, the transvaginal scanning is optimal.
We also offer a comprehensive non-invasive prenatal screening by biochemical and ultrasound screening program for congenital anomalies and chromosomal abnormalities at various stages of pregnancy.
Ultrasound Diagnosis in the First Trimester
Assessment of gestational age by crown rump length. This is particularly important for any women who are unsure of their dates because of irregular periods, conception after recently stopping the pill or whilst on the pill, and conception whilst breast feeding.
Diagnosis of pregnancy from 1 week after the first missed period. It is possible to visualize the gestational sac inside the uterus at this gestation, and confirm an ongoing pregnancy.
Diagnosis of fetal viability from 5.5 –6 weeks. It is possible to detect heartbeat even at this early stage (1.5 –2 weeks after the first missed period), and allows confirmation of a live fetus. Whether the pregnancy is in the uterus, or an ectopic pregnancy can be accurately assessed.
Diagnosis of ectopic pregnancy. A potentially life threatening condition when the pregnancy occurs in the wrong place, early diagnosis of ectopic pregnancy can be made through ultrasound and biochemical tests. Early diagnosis facilitates medical treatment and avoids a surgical operation. Thus appropriate medical or surgical treatment can be planned to avoid danger.
Diagnosis of multiple pregnancy and zygocity. Approximately 2 % of women conceiving spontaneously and 10 -30% of women on fertility treatment will have a multiple pregnancy. At this stage of gestation it offers a unique opportunity to check if the fetuses share a common placenta, as this would have implications to for the rest of the pregnancy.
Screening for chromosomal abnormalities by nuchal translucency scanning between 11-14 weeks. By measuring the fluid behind the neck of the fetus at this stage of pregnancy, in combination with maternal age, we are able to give you a risk for major chromosomal abnormalities which is specific to you, You and your partner can then decide, based on the results, whether it’s high enough to warrant invasive prenatal diagnosis testing which can be chorionic villus sampling or amniocentesis later in the pregnancy.
Diagnosis of some major congenital abnormalities. Some of the major congenital abnormalities can be visualized at this early gestation, and allow for a plan of management to be decided upon.
Ultrasound Diagnosis in the Second Trimester
Fetal anomaly scan involving a detailed systematic survey of the fetus to detect congenital abnormalities and identify anatomical markers for chromosomal abnormalities. It is commonly done between the 18th to 22nd week of pregnancy. It allows major organs to be visualized and assessed as to its function and anatomy.
Doppler blood flow measurement : By measuring the blood flow in the uterine arteries at this stage of gestation, it is possible to pick out a sub-group of patients, which are at increased risk of developing pre-eclampsia and small babies. This allows treatment to commence at an early stage to modify the potential disease.
Placenta Location : A low-lying placenta, which covers the neck of the womb, may be a potential obstacle to a normal vaginal delivery. It may lead to serious bleeding later on in pregnancy endangering mother and baby. In cases where the placenta is visualized to be low at this gestation, we recommend that a scan should be repeated at 34th week, as most placental sites tend to move up and out of the way in late gestation as the uterus increases the size.
Diagnosis of Incompetent Cervix. By measuring the cervical length, it is possible to identify a group of patients who are at risk of premature labor, and it allows special management plan to be made for the pregnancy.
Ultrasound Diagnosis in the Third Trimester
Fetal Growth : The size and weight of the fetus can be determined by measuring a set of parameters. A scan is usually done around 32 - 33 weeks of gestation to screen for small gestational fetuses. Subsequent scans will be planned to monitor their growth.
Fetal Well-being : Ultrasound study of the behavior of the fetus constitutes the Biophysical Profile which is an indication of fetal well being. Together with Doppler Blood Flow we can find out if the fetus is happy and well inside the womb. It allows for an early detection of problems, and allows for treatment to minimize complications, including post delivery problems like cerebral palsy.
Identification of late fetal anomalies. Although relatively rare at this late stage to pick up any abnormalities in the fetus, it is possible that some fetal abnormalities might have been missed in early scans, or that certain conditions might have developed since the last scan.
» Ultrasound Examination of The Breast
An ultrasound of the breast is performed when we need to "look' for different abnormalities of the breast. For example, it is superior when trying to determine whether some lesion is cystic or solid.
By performing Doppler study, we may also be able to determine if there is any abnormal blood flow to the lesion, and aid in the diagnosis of lesions in the breast.
For some women this is required after a mammogram has shown a lesion which is suspicious, for others this maybe the preferred modality for examination.
Ultrasound guided biopsy can also be performed if indicated. Uniquely, The Women's Clinic can perform this under 4D guidance with our state of the art Kretz 730 machine.