Measurement of maternal serum alpha-fetoprotein (MS-AFP) is a useful screening tool for detecting neural tube defects. In cases of elevated MS-AFP, some clinicians and patients choose a sonographic evaluation to avoid the risk of miscarriage associated with amniocentesis. The authors review this use of ultrasound including the types and severity of anomalies that maybe found on Level 1 and Level 2 sonograms.
Alpha-fetoprotein (AFP) screening was shown to be effective for
detecting neural tube defects (NTDs) in the 1970s.
In 1991, the American College of Obstetrics and Gynecology (ACOG)
endorsed offering maternal serum (MS)-AFP testing to all pregnant
women. Since then, screening in the United States became more
wide-spread, and experience in this country and others has
demonstrated considerable benefits from AFP screening, not only for
the detection of NTDs but also for a number of other fetal
abnormalities. Further, even in the absence of multiple gestations
and discrete fetal defects, it is estimated that as many as 20% to
38% of women with unexplained high MS-AFP will suffer adverse
including fetal death,* growth retardation, premature birth, and
While the pathophysiology in these women is poorly understood, it
has been hypothesized that placental ischemia is the underlying
Currently, more than 300,000 pregnant women in California
undergo AFP testing annually. Among the first 1.1 million women
screened through the California AFP Screening Program, 1390 fetal
anomalies (morphologic and chromosomal) were detected (prevalence
of 1.3/1000). These included 710 NTD (417 anencephaly, 247 spina
bifida, and 46 encephalocele), 286 ventral abdominal wall defects,
163 fetuses with Down syndrome, and 231 cases
of other chromosomal anomalies. Impressively, of all anomalies
de-tected in this program, nearly three-quarters involved two organ
systems: the neural axis (51%) and defects of the ventral abdominal
wall (21%). This distribution of "likely" fetal anomalies is
especially germane to the sonologist searching for the cause of
* These fetal deaths occur mainly in the second trimester, and
the risk appears to be directly related to the degree of maternal
serum alpha-fetoprotein elevation.
Alpha-fetoprotein: Where it comes from, how it gets
AFP is a glycoprotein produced initially by the yolk sac and
fetal gut, and later predominantly by the fetal liver. In the
fetus, serum AFP level increases until approximately 14 to 15
weeks, and then falls progressively. In normal pregnancies, AFP
from fetal serum enters the amniotic fluid (in microgram
quantities) through fetal urination, fetal gastrointestinal
secretions, and transudation across fetal membranes (amnion and
placenta) and immature epithelium. Detectable quantities of AFP in
the maternal serum (nanogram quantities) gradually increase during
gestation, peaking at 30 to 32 weeks, and decline thereafter.
Maternal serum levels are usually reported in multiples of the
median (MoM) to standardize interpretation among laboratories.
Abnormal quantities of fetal AFP can enter the maternal serum in
several ways. Among fetal defects, the most common mechanism is
through fetal cutaneous defects, such as anencephaly or
myelomeningocele. These defects result in leakage of fetal serum
proteins into the amniotic fluid and, secondarily, into maternal
serum. Intrinsic placental abnormalities and maternal-fetal
hemorrhage, also allow fetal AFP to mix with maternal serum. In
some cases, the precise mechanism for the fetomaternal transfer is
not known (proximal gut obstruction, renal agenesis), and may be
secondary to diminished fetal gut degradation or elevated fetal
serum concentrations of AFP.
It would be ideal if MS-AFP levels were only elevated in
abnormal fetuses or other pathologic conditions of pregnancy.
Unfortunately, there is considerable overlap in MS-AFP levels
between normal and abnormal pregnancies. Thus, the choice of a
judicious cutoff value, which maximizes detection of anomalies and
minimizes the number of false-positive results, must be chosen for
this screening program to be effective. Many screening programs in
the United States have settled on a serum a value of >= 2.5 MoM.
Using this cut-off, approximately 90% of anencephalic fetuses, 75%
to 80% of fetuses with an open spinal defect, 98% of fetuses with
gastroschisis, and approximately 70% of fetuses with omphaloceles
will be detected.
Further, using 2.5 MoM as the cut-off has resulted in a reasonably
low screen-positive rate (approximately 4% to 5%). Other programs
use a lower cut-off of >= 2.0 MoM, which results in a higher
detection rate of these anomalies, with the trade-off of a higher
MS-AFP screening programs: How patients are
Maternal serum is tested between 16 and 18 weeks. If the MS-AFP
is only marginally elevated (between 2.5 and 3.0 MoM) and the
gestational age is below 17 weeks, the maternal serum may be
retested. Accurate dating is critical for AFP screening because
serum AFP levels rise approximately 15% per week during the 16- to
18-week window. MS-AFP values are also corrected for maternal
weight, race, and the presence of diabetes (diabetes has a
depressing effect on MS-AFP, so lower levels may be found in
association with NTDs).
In California, approximately 2% of screened women have elevated
MS-AFP levels (>= 2.5 MoM), and approximately 3% have MS-AFP
levels ¾ 0.5 MoM. The latter will not be addressed here. Roughly 6%
to 15% of women with high MS-AFP have some type of major congenital
and this risk increases with the magnitude of MS-AFP elevation.
If MS-AFP is elevated, a non-targeted standard antepartum
obstetrical ("Level 1") sonogram is performed for the purpose of
identifying easily recognized causes of "false-positives"
(gestational age >= 2 weeks more advanced than estimated
clinically, multiple gestations, fetal death, and obvious fetal
defects). The intent of a Level 1 sonogram is to provide a general
assessment of fetal/pregnancy health and is performed according to
the published guidelines endorsed by the AIUM and ACR.
Impressively, 20% to 50% of the elevated MS-AFP levels will be
explained by findings on this preliminary sonogram.
If the cause of elevated MS-AFP is not explained, traditionally the
next step has been to offer amniocentesis for measurement of
amniotic fluid (AF)-AFP. Among women who choose to undergo
amniocentesis following a normal Level 1 sonogram, the majority
will have normal AF-AFP (< 2.0 MoM), and there is no further
If the AF-AFP is elevated (>= 2.0 MoM), acetylcholinesterase (an
isoenzyme important in neurotransmission) is tested on the amniotic
fluid sample. Acetylcholinesterase is present in association with
exposed neural tissue (and occasionally with abdominal wall
defects). High AF-AFP plus positive acetylcholinesterase is quite
specific for a fetal defect. In most screening programs, karyotype
testing is also routinely performed on the amniotic fluid
If the AF-AFP is elevated (>= 2.0 MoM), a targeted fetal
sonogram ("Level 2") is offered, because approximately one-third of
fetuses are anomalous.
Similar to MS-AFP, the likelihood of a fetal defect increases
proportionately with the degree of AF-AFP. The Level 2 sonogram is
performed in these cases to determine: 1) whether any fetal anomaly
is present: (elevated AF-AFP may be false-positive); 2) if present,
what the nature of the anomaly is (i.e., NTD versus omphalocele);
and 3) if present, the severity of the anomaly (i.e., the spinal
level of the myelomeningocele) and to search for other
AF-AFP testing is a highly sensitive method for detecting or
excluding NTDs. The negative predictive value of a normal AF-AFP is
approximately 97% and elevated AF-AFP plus acetylcholinesterase
allows > 99% accurate detection of NTD.
Targeted ultrasonography performed in conjunction with abnormal
AF-AFP is also highly accurate in identifying anomalous fetuses
(i.e., >99% accurate).
However, there is a small but important procedural fetal loss rate
associated with amniocentesis, generally quoted to be approximately
1/200 (0.5%), which is not present with the sonographic
examination. As a result, women with elevated MS-AFP, in increasing
numbers, opt to go directly from the serum AFP test to a targeted
fetal sonogram (i.e., to skip the amniocentesis). Indeed, this
method has been adopted in the United Kingdom and detailed,
targeted sonograms are now routinely performed as the next step in
women with high MS-AFP. This approach has become more popular in
the last few years for two major reasons. First, sonographic
detection of the "likely" anomalies associated with high MS-AFP is
currently highly accurate. Expected rates of sonographic detection
for neural tube and abdominal wall defects are currently >90%
(several series report 100% detection rate for NTDs).
It is estimated that a complete, detailed, normal sonogram can now
reduce the MS-AFP-based risk of a neural tube or ventral abdominal
wall defect by 95%.
Second, going directly to Level 2 sonography circumvents the small
but important procedural risk of fetal loss from amniocentesis. It
has been suggested that the slightly higher diagnostic yield of
amniocentesis (as compared to ultrasound) may not be justified,
given both the higher cost and procedure-related fetal loss rate
associated with this approach.
Some have cautioned against adopting a routine policy of
circumventing the amniocentesis
because: 1) this approach will require a much larger number (i.e.,
ten times as many) of targeted sonograms, and the larger number of
experienced examiners may not be available or patients may be
required to travel a long distance for the targeted sonogram; 2)
that even "experienced" examiners, scanning a population with a
lower prevalence of defects may not detect as many defects as
and 3) skipping amniocentesis will cause potentially detectable
chromosomal abnormalities to be missed. The last issue remains
controversial. Some favor a paradigm in which Level 2 sonography
follows a high MS-AFP, arguing that there is only a very small risk
of an abnormal karyotype in a fetus without morphologic defects. If
the targeted sonographic fetal survey in a woman with elevated
MS-AFP is normal, it has been estimated that the risk of a fetal
chromosomal abnormality is only 0.6% to 1.1%,
and of the chromasomally abnormal fetuses, sex chromosome
aberrations (other than 45X) account for many (30% to 50%).
There is no "right" choice, but all women facing the choice of
Level 2 sonography versus amniocentesis should be fully informed of
these controversies during their counseling. Decisions to do
amniocentesis versus Level 2 sonography will vary according to
patient (maternal age, other seriologic markers [i.e., hCG,
estriol], and personal choice) and institution (depending on
availability of experienced sonologists). Amniotic fluid testing
should still be strongly considered in the following patients: 1)
fetal position or maternal body habitus precludes an adequate
sonographic fetal anatomic survey; 2) equivocal sonographic
findings (i.e., abnormal posterior fossa but spinal defect not
seen); 3) experienced sonographic examiner not available; and 4)
non-lethal anomaly detected on Level 1 sonogram, for which
karyotype testing is appropriate.
Increased MS-AFP: What should you look for?
The neural axis and ventral abdominal wall will be the most
critical regions under scrutiny during the Level 2 sonogram. A
focused examination of the neural axis in each fetus should include
an assessment of overall cranial size and contour, ventricular size
(transaxial diameter of ventricular atrium >10 mm is abnormal),
posterior fossa including cerebellar morphology, and cisterna
At UCSF, we also include images of the cavum septum pellucidum as a
check for forebrain malformations. The spine should be carefully
examined in each fetus, including segment by segment images in the
transaxial and sagittal planes from the craniocervical junction
through the sacrum. The normal curvature of the spine and intact
dorsal skin line should be documented and the ossified posterior
elements should be examined for abnormal splaying. The ventral
abdominal wall of the fetus is examined with focused attention on
the umbilical cord insertion. The examiner should maintain a
heightened sensitivity to the presence of bowel loops within the
umbilical cord or floating in the amniotic fluid distant from the
cord insertion/abdominal wall.
The most commonly encountered individual defects are discussed
Anencephaly--Anencephaly accounts for approximately half of all
NTDs (figure 1). On average, anencephaly is associated with the
highest AF-AFP and MS-AFP values of all NTDs, and approximately 90%
will be detected by an MS-AFP >= 2.5 MoM. This is a lethal
anomaly in which the bony calvarium is absent above the orbits.
Normal cerebral cortex is absent. Some dysplastic "brain tissue"
histologically representing angiomatous stroma, may be observed
above the orbits, apparently floating freely in the amniotic fluid.
Owing to its irregular shape and the absence of recognizable normal
morphology, it is unlikely to be confused for normal brain. One
should be cautious, however, not to confuse an engaged fetal head
(in which the convexity may not be well visualized) for
anencephaly. This is accomplished by the observation of amniotic
fluid above the orbits and the calvarial defect. It is critical
that this diagnosis is accurate because most patients will
electively terminate their pregnancies following this diagnosis.
Anencephaly can be diagnosed in virtually all affected fetuses
after 14 weeks gestation.
Myelomeningocele--Myelomeningocele occurs in approximately
1:1000 live births in California (incidence is slightly higher in
the southeastern United States). The myelomeningocele sac can be
detected on sagittal or transverse views. Even in the absence of a
sac, myelomeningocele is suggested by a defect in the normal smooth
dorsal skin line and splayed posterior ossification centers on the
transaxial image (figure 2). Widening of the posterior ossification
centers can also be seen on coronal images of the spine. The
majority of spinal dysraphisms occur in the lumbosacral region, so
this area should be scrutinized with extra care. Very abnormal
spine curvature may be associated with the amniotic band syndrome
or limb body wall complex. When the fetus is in breech
presentation, endovaginal scanning can be helpful.
Spinal defects can be small and inconspicuous. This is
undoubtedly the reason that sonographic detection was only mediocre
(50% to 80%) in reports from the early 1980s.
Descriptions of several important cranial findings associated with
"open" spina bifida have been tremendously beneficial for improving
the sensitivity with which spina bifida is detected antenatally.
Cranial findings associated with "open" (non-skin covered) fetal
myelomeningoceles include the "lemon sign,"
effaced cisterna magna,
and small biparietal diameter (BPD).
At least one of these findings is present in >99% of affected
The lemon sign (figure 3A) describes an inward scalloping of the
frontal cranial bones seen in nearly all second-trimester fetuses
with open spina bifida, but tends to disappear in affected fetuses
in the third trimester. Importantly, the lemon sign may also be
seen in as many as 1% of normal fetuses
in addition to a number of other neural axis anomalies diminishing
its positive predictive value for spina bifida.
Thus, the diagnosis of spina bifida should never be based solely on
the observation of a lemon sign.
The banana sign (figure 3B) and the effaced cisterna magna occur
secondary to the hindbrain malformation known as the Chiari II
malformation, which is present in almost all (>95%) fetuses who
have open spinal lesions. The bony posterior fossa is small in the
Chiari II malformation and the developing cerebellum is cramped.
The crowded cerebellum appears to wrap around the brain stem
(creating a transaxial cerebellar configuration akin to the shape
of a banana) or, at the minimum, the cisterna magna is completely
or nearly obliterated. The banana sign is highly specific for the
Chiari II malformation but not quite as sensitive as effacement of
the cisterna magna (some of the posterior fossa deformities of the
Chiari II malformation are not severe enough to produce a banana
cerebellum). Effacement of the cisterna is more sensitive for
detection of the Chiari II malformation, but less specific (it can
be seen in association with hydrocephalus). The cisterna magna (3
to 10 mm) can be visualized in 97% of normal fetuses at 15 to 25
weeks gestation. Because the Chiari II malformation (and
myelomeningocele) is nearly always associated with an
abnormal-appearing posterior fossa, a small or absent cisterna
should raise suspicion for a spinal lesion. As a corollary, a
normal-appearing cerebellum and cisterna magna, has a high
(>98%) negative predictive value for the Chiari II malformation.
Thus, a normal-appearing posterior fossa reduces the risk of an
open spinal lesion by >98%.
Other cranial findings associated with spina bifida include a
BPD which is small for dates (second trimester) and ventricular
enlargement. The degree of ventricular dilatation in fetuses with
myelomeningoceles tends to increase with gestational age.
In a series of 51 fetuses with spina bifida aperta
(nonskin-covered), we found ventriculomegaly (atrium >10 mm) was
present in only 44% of myelomeningocele fetuses examined before 24
weeks, but present in 94% of fetuses scanned in the third
The degree of ventriculomegaly is also related to the degree of
visualized posterior fossa deformity,
but not to the spinal level of the lesion.
It should be emphasized that even though the cranial findings have
so greatly improved the sensitivity with which we can detect
myelomeningocele (currently reported to be >90% and >95% in
the final diagnosis of a myelomeningocele should only be made after
direct observation of the spinal defect.
If a myelomeningocele is detected
Outcome of fetuses with mye-lomeningocele is influenced by the
presence of associated malformations, chromosomal abnormalities,
the level of the spinal lesion (children with higher lesions have
more severe motor handicaps), and childhood shunt infections.
Prenatal sonography can offer important and accurate information
regarding the presence of ventriculomegaly, the level of the spinal
lesion, and the presence of associated malformations. The bony
level of the defect can be accurately estimated (± one spinal
level) sonographically in 79% of fetuses.
This is accomplished in most cases by "counting up" from the last
sacral ossification center (assumed to be S4 in the second
trimester and S5 in the third). Associated malformations (in
addition to the Chiari malformation and hydrocephalus) are present
in 13% to 24% of fetuses with myelomeningocele.
Multiple malformations increase the likelihood of fetal karyotype
but chromosomal abnormalities are reported in 10% to 15%
of fetuses with "isolated" myelomeningocele. Thus, if the parents
plan to carry the pregnancy, it is prudent not only to perform a
complete, detailed, fetal anatomic survey but also to offer fetal
Cephalocele--Cephaloceles are relatively rare (1.2/10,000
births), midline cranial defects that contain meninges,
cerebrospinal fluid (meningocele), ± neural tissue (encephalocele).
These lesions only account for approximately 3% of fetal anomalies
detected with MS-AFP screening and 6% of detected NTDs.
In the United States, most (80% to 85%) of these occur in the
a small percentage occur in the frontal (10% to 15 %) or parietal
(10 to 15%) area. Because encephaloceles occur in the midline,
off-midline cranial defects should suggest the presence of the
amniotic band syndrome. Most occipital lesions are associated with
abnormalities of the posterior fossa and parietal lesions may also
be associated with the Chiari malformation. The face and orbits
should be examined carefully. The interorbital distance is usually
widened in association with a frontal encephalocele.
Prognosis of fetuses with cephalo-celes is generally poor (only
21% live-born in our series)
and outcome is related to the presence of associated neural and
non-neural malformations (common), as well as the size and content
of the lesion. Poorer outcome is associated with a large volume of
herniated brain. Associated brain malformations include the
Dandy-Walker malformation, agenesis of the corpus callosum,
cerebellar hypoplasia, and migrational abnormalities. Karyotype
abnormalities are common, found in 44% of tested fetuses in one
It is important to remember that many encephaloceles are
skin-covered (60% in one series)
and, therefore, may elude detection with MS-AFP screening.
Occipital cephaloceles may occur as part of the heritable
(autosomal recessive) Meckel's syndrome (encephalocele, cystic
dysplastic kidneys, and polydactyly).
Affected pregnancies may be terminated without adequate pathologic
diagnosis. Therefore, prenatal recognition of this potential
syndromic association is important for counseling regarding future
pregnancies, because the 25% risk of recurrence associated with
Meckel syndrome greatly exceeds the recurrence risk of other
Ventral abdominal wall defects--Ventral abdominal wall defects
include omphalocele, gastroschisis, and abdominal wall defects
associated with the amniotic band syndrome or limb body wall
complex. Scrutiny of the fetal umbilical cord insertion and ventral
abdominal wall allows sonographic detection of omphalocele and
gastroschisis in >90% of fetuses.
Omphaloceles occur in approximately 1:4,000 live births, and
include a spectrum of midline defects that range from large
(usually containing liver and bowel) (figure 4) to small (which may
contain only 1 or 2 bowel loops). The exteriorized viscera are
contained by an anu-amnioperitoneal membrane, and the umbilical
cord inserts midline into the sac. Features most predictive of
prognosis are other serious malformations (expected in 50% to 75%
of affected fetuses, including cardiac malformations in 30% to 35%)
and chromosomal abnormalities (approximately 10% to 20%), mainly
trisomies 18 and 13. Although "bowel-only" omphaloceles are
generally smaller, less conspicuous sonographically, and often
easier to repair postnatally, the rate of chromosomal abnormalities
(perhaps 70% to 80%) is 8 to 10 times higher than that found in
fetuses in whom the omphaloceles contain liver within herniated
Be aware that small bowel-only omphaloceles may contain only one or
two loops of bowel that have migrated into the cord so that the
abnormality may not be recognized solely by examination of the cord
insertion into the fetal abdomen. Thus, examination of the
umbilical cord beyond the fetal abdomen for several centimeters is
Gastroschisis is a full-thickness, paramedian, abdominal wall
defect, usually occurring to the right of the fetal umbilical cord
insertion, through which bowel is exteriorized. Importantly, there
is no covering membrane (figure 5). Associated malformations other
than gut malrotation and atresia are rare, and the prevalence of
chromosomal abnormalities is not increased. Fetal growth
retardation is seen in up to 40%.
Bowel dilatation and mild thickening is common as gestation
progresses and loosely correlates with seriously damaged bowel
requiring resection postnatally.
Early in the second trimester (<20 weeks), gastroschisis may be
difficult to observe. The defect in the abdominal wall is small (1
to 3 cm) and, early on, the bowel is usually nondilated.
A large population-based study involving 72,782 consecutively
screened pregnancies was used to establish distributions of AFP in
pregnancies with gastroschisis and omphalocele.
Based on a cut-off of 2.5 MoM, all fetuses with gastroschisis
(20/20) and approximately 70% (10/18) of omphaloceles were detected
during MS-AFP screening.
Less commonly observed fetal defects associated with elevated
MS-AFP--A number of other important fetal anomalies are associated
with elevated MS-AFP, and these potential defects should also be
sought on the targeted sonogram. Less common defects include fetal
teratoma (pharyngeal, sacral), defects caused by the amniotic band
syndrome (asymmetric cephaloceles, gastropleuralschisis), cystic
hygroma, lesions that alter the placentomaternal barrier (i.e.,
placental chorioangioma, lakes, and abruption/ hemorrhage),
proximal fetal gut obstructions (i.e., esophageal and duodenal
atresias), some renal abnormalities
(including multicystic dysplastic kidney, pelviectasis, congenital
or Finnish nephrosis), and oligohydramnios. Thus, careful
examination of the face, posterior neck, oropharynx, thorax, and
abdomen (including a normally filled stomach) should be performed.
The limbs and digits should be assessed for abnormalities
suggesting the anu-amniotic band syndrome or VACTERL (vertebral,
anorectal, cardiac, tracheoesophageal fistula, renal, and limb
anomalies) association. Amniotic fluid volume should be
qualitatively or semiquantitatively assessed in addition to careful
examination of the placenta.
The AF- and MS-AFP may be elevated in fetuses with cystic
hygroma (CH). While the precise mechanism is not known, it is
speculated that fetal serum proteins may leak through the
membrane/integument covering the CH, or perhaps enter the maternal
blood through an intrinsic placental abnormality associated with an
abnormal karyotype (present in 60% to 80% of second- and
third-trimester fetuses with CH).
Teratomas (most commonly sacral [figure 6], but also
oropharyngeal and lingual) can grow to a very large size in fetal
life. These tumors often ulcerate, allowing leakage of fetal
protein into the amniotic fluid and, secondarily, into maternal
serum. In many cases, they are not completely skin-covered.
Transverse axial views of the oropharynx, coronal and axial views
of the face (to exclude oropharyngeal and lingual teratomas), and
transverse and longitudinal views of the sacral area
(sacrococcygeal teratomas are most common) should be obtained in
patients referred for elevated MS-AFP. How sensitively teratomas
are detected by MS-AFP screening is not known.
Esophageal atresia and duodenal atresia have been associated
with elevated AFP. Some have speculated that a smaller than average
degradation of swallowed AFP might account for the AFP elevation. A
normally filled fetal stomach and the absence of a persistently
filled or dilated duodenum should be sought. The normal fetal
duodenum empties immediately and a persistently filled duodenum
(even if it does not appear "over-distended") is always abnormal.
The presence of a fetal "double bubble" suggests duodenal
obstruction (usually atresia, but can be due to stenosis, Ladd's
bands, or annular pancreas). Importantly, nearly one-third of
fetuses with duodenal atresia have Down syndrome. Thus, if a double
bubble is detected, a focused examination of the fetal heart is
performed and karyotype testing is offered to the parents.
Esophageal atresia is suggested by an absent/unfilled stomach
and polyhydramnios; but this constellation of observations is
insensitive (<50%) for the sonographic detection of fetal
esophageal atresia before the third trimester. This is due to the
fact that the proximal esophageal pouch is only rarely seen in
fetuses, and a fistula exists between the lower esophagus and
bronchial tree in >90%, allowing passage of some fluid into the
fetal stomach. A small, not absent stomach was observed in 5 of 12
fetuses with proven esophageal atresia by McKenna et al.
In addition, frank polyhydramnios, is typically not seen before 20
to 24 weeks gestation.
Renal abnormalities including congenital (Finnish) nephrosis,
multicystic dysplastic kidney, renal agenesis, and pelviectasis
have been associated with elevated MS-AFP.
In some cases, the AFP is elevated secondary to abnormal leakage of
proteins into fetal urine. Congenital nephrosis results in a
dramatic fetal proteinuria in utero and, because there are no renal
morphologic features, this is a very difficult diagnosis to make
with certainty antenatally. The clue to the diagnosis is that both
the MS- and AF-AFP levels are extremely high (i.e., typically >=
10 MoM!) with negative amniotic fluid acetylcholinesterase and
without evidence of maternal-fetal hemorrhage or other fetal
In cases of renal agenesis, the mechanism for MS-AFP elevation is
not known, but it is speculated that these fetuses may have higher
serum protein levels owing to diminished excretion.
Finally, placental abnormalities including chorioangioma,
placental abruption, periplacental hemorrhages (i.e., subchorionic
hemorrhage), and placental lakes may result in elevated MS-AFP. A
careful examination of the placenta should be performed.
Relatively minor placental abnormalities (i.e., placental lakes,
large marginal veins) are seen commonly in pregnancy patients.
Although the placenta should be carefully examined in all women
referred for high MS-AFP, this placental lesion should be the
diagnosis of exclusion (after morphologic defects have been
excluded), as the cause of increased MS-AFP. AR