1. Alpha-fetoprotein (AFP) and maternal serum AFP (MSAFP)
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1. A raised MSAFP level at 16 weeks
a. | may be due to incorrect assessment of gestation. | True |
b. | may be due to gastroschisis. | True |
c. | is more likely with multiple pregnancy. | True |
d. | is more likely after threatened miscarriage. | True |
e. | is more likely in Afro-Caribbeans | False |
f. | is more likely in women with diabetes. | True |
g. | is more likely in women with antiphospholipid syndrome | True |
h. | is more likely if the fetus has T18. | False |
i. | is more likely if the fetus has T21. | False |
j. | is more likely with fetal parvovirus infection | True |
k. | should trigger a repeat test as soon as possible after 7 days | False |
l. | should be investigated by amniocentesis. | False |
k. There is no point in repeating the test - why believe a
different result?
2. A raised MSAFP level at 16/52 with a normal scan at 20/52 is linked to an increased risk of:
m. | intra-uterine growth restriction | True |
n. | premature labour. | True |
o. | placental abruption. | True |
p. | abnormal placental adherence: accreta and percreta. | True |
q. | gestational diabetes. | False |
r. | fetal cleft lip | False |
3. Serum Alphafetoprotein:
s. | is not present in those who are not pregnant. | False |
t. | Caucasians have higher levels than Afro-Caribbeans in pregnancy. | True |
u. | is raised in women on the Pill. | False |
background
parvovirus
consequences of raised MSAFP for the normal baby
MSFP and anti-phospholipid syndrome
AFP | alpha-fetoprotein |
APS | anti-phospholipid syndrome |
BMI | body mass index |
DOH | Department of Health |
DRCOG | Diploma of the RCOG hDiploma of the RCOG |
DS | Down's syndrome |
FTCS | first trimester combined screening |
G6PD | glucose-6-phosphate dehydrogenase deficiency |
hCG | human chorionic gonadotrophin |
IDDM | insulin-dependent diabetes mellitus |
IUGR | intra-uterine growth restriction / retardation |
MCQ | multiple-choice question |
MOET | Managing Obstetric Emergencies and Trauma |
MRCOG | Membership of the RCOG |
MSAFP | maternal serum AFP |
NICE | National Institute for Health and Clinical Excellence |
NSC | UK National Screening Committee |
NT |
nuchal translucency. |
NTD | neural tube defect |
OSCE | objectivem structured, clinical examination |
PAPP-A | pregnancy-associated plasma protein A |
RCOG | Royal College of Obstetricians and Gynaecologists |
T18 | trisomy 18 |
T21 | trisomy 21 see MCQ paper 6, question 24 |
UKNSC | UK National Screening Committee |
Go to the bottom of the page & links to other pages.
You are likely to get a question about MSAFP in the MCQs.
It will usually be about things associated with a raised or reduced MSAFP value.
It could even be about elevated levels & the non-pregnant.
The following
tells you all you need to know and probably a bit more.
Go to the bottom of the page & links to other pages.
Is AFP still of clinical significance?
AFP has been of fluctuating significance in O&G.
It was the basis of screening for neural tube defects (NTDs) and Down's syndrome (DS).
Ultrasound scanning has replaced it for screening for NTDs.
This left it with a role in biochemical screening for DS in the second trimester.
But screening for DS has now moved to the 1st. trimester: "combined 1st. trimester screening".
This involves a scan for nuchal translucency and blood tests for PAPP-A and hCG, but not AFP.
I tell
you this now to start the process of cementing it in your head, but it will be
discussed again later: MCQ4, question 26, MCQ6, question 24 and MCQ11, question
10.
So, AFP is left with a much diminished role:
biochemical screening for those who book too late for the preferred 1st. trimester DS screening
and as a
tumour marker in a number of cancers.
Go to the bottom of the page & links to other pages.
Exam questions will usually be about maternal serum AFP.
You are likely to get a question about it the MCQs in both DRCOG and MRCOG.
It will usually be about a high or low MSAFP.
But you could be asked about elevated levels in the non-pregnant.
The
following tells you all you need to know and probably a bit more.
Note the scope for tricky
questions.
Background levels of MSAFP are higher in Afro-Caribbean women than in Caucasians.
But, perversely, Afro-Caribbean women have a lower incidence of NTDs than Caucasians.
Laboratory reports must take this into account.
Once the levels are corrected for ethnicity, Afro-Caribbean women have a reduced risk of a high result as they have a reduce risk of NTD.
The converse is true of women with IDDM and obesity who have higher risk but lower levels of MSAFP..
More of this
below, but it means reading the question carefully.
Go to the bottom of the page & links to other pages.
First of all, is the test result reliable?
MSAFP levels and their
interpretation are affected by:
gestation,
diabetes,
high or low
and
ethnicity.
Raised MSAFP:
The biggest link is with
neural tube defect.
but other abnormalities cause
increased values:
abdominal
wall defects
and upper gut
atresias.
there are various benign
causes of high values:
dates errors,
bleeding,
multiple
pregnancy etc. - see below.
Raised MSAFP but no obvious explanation such as fetal anomaly:
There is a
risk of fetal and placental problems in late pregnancy:
IUGR,
placental
abruption,
premature
labour,
placenta
accreta and percreta.
and an association with anti-phospholipid
syndrome.
Low MSAFP
Is associated with chromosomal abnormalities, particularly T21 and T18.
Raised
These are found in cirrhosis,
liver cancer, some germ-cell tumours etc.
Expanded information for the MRCOG and to help facts stick for the DRCOG.
You probably don’t need to know more than what is above, but the following might just help it stick.
Don’t worry about the references; they are included for those
who might want to look at original paper.
The fetus produces large amounts of
Fetal levels are maximal at about 12 – 14 weeks, but MSAFP levels continue to rise, peaking in the third trimester
By the 1970s, raised
Leighton et al. 1975. Lancet, 1975. Vol 306, Issue 7943, P 1012 - 1015.
Screening programmes based on raised MSAFP were rapidly introduced.
But things move on and by the 1980s, ultrasound scanning had become very accurate in screening and diagnosing anencephaly and NTDs.
AFP-based screening for NTDs was phased out and it looked as though it would become of historical interest only.
Then, in 1984, Cuckle et al published the link between low MSAFP and DS. Lancet, 1984 Vol 323, Issue 8383, P 926 - 929.
Merkatz et al, also in 1984, described a case of "undetectable" MSAFP in a pregnancy that resulted in a baby with trisomy 18.
They did a retrospective survey of >3,000 pregnancies and identified 32 pregnancies resulting in trisomy.
All of these pregnancies had low MSAFP. Am J Obstet Gynecol. 1984 Apr 1;148(7):886-94.
This created a new life for
The history is interesting, but you are not going to be asked in the DRCOG.
You might quote it in a MRCOG OSCE viva if you are going for
the gold medal.
What is AFP's
role?
.We have no clear idea of what
Some say it is the fetal equivalent of adult albumin.
Others that it has a role in the immunological interplay between mother and baby.
But there is a rare genetic abnormality leading to failure of production of AFP and the babies develop normally.
Sharony, Zadik & Parvari R. Eur J Hum Genet. 2004 Oct;12(10):871-4.
No one is going to ask for your opinion or this level of
detail in the DRCOG and you would be a shining star to quote this in the MRCOG!
Levels in the neonate fall rapidly and only minimal amounts are present after 6 months.
It is detectable in the non-pregnant but in miniscule amounts.
Levels rise in a variety of conditions:
cirrhosis,
liver cancer,
acute and chronic hepatitis,
ovarian and testicular germ cell tumours
and some bowel cancers.
In some of these it is used as a tumour marker.
For further data go to:
http://www.medicinenet.com/alpha-fetoprotein_blood_test/article.htm.
Small amounts of AFP get into the amniotic fluid and even smaller amounts into the maternal circulation.
MSAFP levels rise steeply during the second trimester.
When checking values, careful dating is essential.
I refer to gestation assessment, not social encounters, though I might have some fatherly advice about those too.
Anything that breaches the fetal skin allows more AFP to leach into the liquor.
Hence neural tube and abdominal wall defects cause higher than normal levels.
Levels are increased with twins, bleeding in early pregnancy and invasive procedures such as amniocentesis.
The fetus gets rid of some AFP by swallowing liquor, so upper gut obstructions are associated with raised levels.
There are also rare conditions such as congenital nephrosis and placental or cord tumours.
In the group of rare causes is parvovirus infection. (See MCQ paper 5, question 36.)
More small print stuff!
The main problem with this virus is bone marrow suppression and anaemia that can be bad enough to kill.
Some affected pregnancies will have raised MSAFP.
This only occurs in a minority of the pregnancies and not early enough to allow intervention.
So, it is no use as a screening test for the severe fetal anaemia which is the main worry.
It might interfere with second trimester biochemical screening for Down’s syndrome (see MCQ paper 4, question 26 and MCQ paper 6, question 24).
Particularly as some of these babies will also have a raised maternal hCG.
You won’t be asked about this in the DRCOG exam.
Even in the MRCOG it would only be one mark in a MCQ.
Raised MSAFP: consequences for the normal baby.
There is an increased risk of
IUGR,
placental abruption,
premature labour
and placenta accreta and percreta
in pregnancies with a normal baby but a raised MSAFP,
presumably reflecting impaired placentation.
This is ill-understood, but it is important as it is common.
The assumption is that some form of failure of placentation allows increased AFP transfer to the mother.
And that the abnormal placentation subsequently manifests itself in the risk of IUGR etc.
(See also MCQ 2, question 3 and MCQ 10, question 1.)
The risk of IUGR increases up to tenfold, in proportion to
the degree of elevation of
But even with slight increases
these are high-risk pregnancies.
A raised MSAFP is also found in association with APS.
This is thought to reflect placental damage caused by thrombosis.
There is a good case for antenatal clinics to have a protocol
for the management of raised MSAFP with no identified fetal anomaly.
The association with placenta accreta and percreta is not
well known, but was first described in the early 1990s. Ginsberg et al.
described the first case in 1992.
J Assist Reprod Genet. 1992 Oct;9(5):497-500.
McDuffie et al reported a dramatic case with acute abdomen at 17 weeks due to haemoperitoneum.
The patient had had a MSAFP of 5 MOM the previous week.
Am J Obstet Gynecol. 1994 Aug;171(2):565-6.
Knowledge of the association is likely to improve as it is highlighted in the MOET Course Manual.
The importance for the MRCOG candidate is that the association is likely to be in the MCQ database.
Even more important, you would be deemed negligent if a patient with a high MSAFP came to harm from placenta accreta or percreta because the diagnosis had not been considered and appropriate steps taken to diagnose and treat it.
There is a good review article on the internet:
http://www.obgmanagement.com/article_pages.asp?AID=2963&UID=.
What factors influence the
interpretation of the results?
Diabetes.
Patients with IDDM are at increased risk of fetal abnormality, including neural tube defects, which are several times more common.
Perversely, they also tend to have lower than average MSAFP levels (by 10-20%).
Test results must be interpreted with this in mind.
Being Afro-Caribbean.
Afro-Caribbeans have about half the risk of neural tube defect of Caucasians.
But higher normal MSAFP levels (10-15%).
To digress: questions about the prevalence of different hereditary conditions in various ethnic groups can be crop up.
As a rule of thumb, Ashkenazy Jews
have the highest incidence and Afro-Caribbeans the lowest, if one takes out
sickle cell anaemia and
G6PD.)
Maternal weight.
Maternal weight also influences MSAFP interpretation.
Overweight women having lower than normal levels and thin women raised levels.
The simple explanation is that the bigger the woman, the greater the blood volume and degree of dilution of AFP.
Extremes of weight lead to appropriate interpretation by the laboratory.
You don’t need to remember all the percentages, that’s for the MRCOG.
But you should know the various links.
The standard form for MSAFP tests includes a reminder to mention diabetes, ethnic background and weight.
This allows the laboratory to use the correct reference
values.
MSAFP and screening for Down's syndrome.
Screening for Down
Both the DOH’s NSC and NICE have recommended this with implementation by 2010.
All screening does is give an estimate of the woman’s risk of
having a baby with DS. It starts with the risk derived from maternal age.
Different authorities give slightly different numbers. Here
are four easy-to-remember ones.
Maternal age |
Risk of Down’s syndrome |
20 |
1 in 1,500 |
35 |
1 in 350 |
40 |
1 in 100 |
45 |
1 in 40 |
Screening by maternal age.
In ancient times, this was all we had to quantify risk.
Most units had a policy of offering amniocentesis to women ≥ 35 years.
This was not very good.
Most babies with DS are born to women < 35 years, as most babies are born to younger women.
So, this policy missed most babies with DS, i.e. its sensitivity was low.
In addition, women of 35, whose risk was only 1 in 350 were
being offered amniocentesis which has a 1 in 100 risk of causing miscarriage.
2nd. trimester biochemical screening.
This has been the mainstay of screening for decades.
The age-derived risk is refined by adding other measurements.
MSAFP was added – the lower the level, the greater the risk of DS.
Further refinement was brought with the addition of assay of hCG, oestriol and inhibin.
The test is usually done at 16 weeks and after a scan has been done for gestation.
This is a significant disadvantage, meaning that termination of any affected pregnancy has to be done by inducing labour.
And the woman has to go through the horrors of that and
delivery.
1st. trimester combined screening.
The UKNSC recommended that from April 2010 screening for DS should be done in the first trimester.
Increased NT is associated with higher DS risk and is the key component of FTCS. (MCQ paper 10, question 35).
Screening gets even better when you add 1st. trimester maternal biochemistry:
serum PAPP-A (MCQ paper 3, question 36)
and beta-hCG levels (MCQ paper1, question 33).
FTCS obviates the horrors of late
termination of affected pregnancies.
Second trimester serum screening will remain for those who book too late for first trimester screening.
In real-life counselling you give the facts in as emotionally-neutral a fashion as possible,
But I like to point out that even at the age of 45 there are 39 chances in 40 that the baby does not have Down’s syndrome.
Older women getting pregnant are having a bad time now because of publicity about the risks.
Don’t add to their potential worry and guilt by exaggerating
them.
Remember that no screening test is perfect and that all of them lead to normal pregnancies being lost after amniocentesis.
This is a terrible price to pay for having a test! (see MCQ4,
question 2 and MCQ8 question 16).
MSAFP is also lower in T18 (See MCQ2, question
35). T18 and T21 are the only conditions associated with
low MSAFP levels (apart from the rare congenital absence of
creening for Down's syndrome has now moved to the first trimester.
Both the DOH’s NSC and NICE have recommended this with implementation by 2010.
Programmes will be based on 1st. trimester nuchal translucency (MCQ paper 10, q. 35).
To this will be added 1st. trimester maternal biochemistry: serum PAPP-A and beta-hCG levels.
This is called 1st. trimester combined screening.
This will obviate the horrors of late termination of affected pregnancies.
Second trimester serum screening will remain for those who book late.
So AFP will not be relegated to the history books quite yet.
Some argue that it should be retained as a predictor of IUGR even if first trimester combined screening has been done for aneuploidy.
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