Screening for Down Syndrome
Recommendation
The offering of amniocentesis or chorionic
villus sampling (CVS) for chromosome studies is
recommended for pregnant women at high risk for Down syndrome. The offering of screening for Down syndrome by serum multiple-marker
testing is recommended for all low-risk pregnant women, and as an alternative
to amniocentesis and CVS for high-risk women (see Clinical
Intervention). This testing should be offered only to women who are seen for
prenatal care in locations that have adequate counseling and follow-up
services. There is currently insufficient evidence to recommend for or against
screening for Down syndrome by individual serum marker testing or ultrasound
examination, but recommendations against such screening may be made on other
grounds (see Clinical Intervention).
Burden of Suffering
Down syndrome, a congenital syndrome caused by trisomy
of all or part of chromosome 21, is the most common chromosome
abnormality.1 Population-based surveillance programs have reported a Down syndrome
birth prevalence of 0.9/1,000 live births.2 The incidence of Down syndrome is higher than the birth prevalence,
however, since many fetuses are spontaneously aborted, some are recognized in utero and electively aborted, and some cases are not
recognized at birth. Affected children are characterized by physical
abnormalities that include congenital heart defects and other dysmorphisms, and varying degrees of mental and growth
retardation. Although there are therapies for some of the specific
malformations associated with Down syndrome, there are no proven therapies
available for the cognitive deficits. Life expectancy for infants born with
Down syndrome is substantially lower than that of the general population.3 Based
on 1988 cross-sectional data, the lifetime economic
costs of Down syndrome have been estimated to be $410,000 per case.4
The risk for Down syndrome and
certain other chromosome anomalies increases substantially with advancing
maternal age.1,5-10
Parents carrying chromosome-21 rearrangements are also at an
increased risk of Down syndrome pregnancies,11-13 with
the risk being much higher if the mother carries the rearrangement than if the
father does. Also at higher risk are those who have previously had an affected
pregnancy, independent of advancing maternal age and chromosome rearrangements.14,15
Accuracy of Screening Tests
Down syndrome is diagnosed prenatally by determining karyotype in fetal cell samples obtained by amniocentesis
or chorionic villus
sampling (CVS). Because of their invasiveness, risks, and cost, these
procedures are generally reserved for women identified as high-risk either by
history (i.e., advanced maternal age, prior affected pregnancy, known chromosome
rearrangement) or by screening maneuvers (e.g., serum markers, ultrasound).
Chromosome analysis of fetal cells obtained by second-trimester amniocentesis
has been demonstrated to be accurate and reliable for prenatal diagnosis of
Down syndrome in a randomized controlled trial and several cohort studies.16-19 CVS, a
technique for obtaining trophoblastic tissue, is an
alternative to amniocentesis for detecting chromosome anomalies. The advantages
of this procedure include the ability to perform karyotyping
as early as 10-12 weeks and more rapid cytogenetic analysis.
Potential disadvantages of CVS include apparent discrepancies between the karyotype of villi and the fetus
due to maternal cell contamination or placental mosaicism,
and failure to obtain an adequate specimen, resulting in a repeat procedure
(usually amniocentesis) in up to 5% of tested women.20-22 In
randomized controlled trials20-22 and
cohort studies23-29 comparing CVS to amniocentesis, accurate prenatal diagnosis has been
obtained in over 99% of high-risk women when CVS is accompanied by both direct and culture
methods of cytogenetic examination and when
amniocentesis is provided to clarify CVS diagnoses of mosaicism
or unusual aneuploidy. Transabdominal
CVS has been reported to have comparable accuracy to transcervical
CVS in randomized controlled trials.20,30,31
First-trimester amniocentesis (at 10-13 weeks)
has been compared to CVS in one randomized controlled trial.32
Success rates were the same for the two procedures (97.5%);
early amniocentesis failures were primarily due to failed culture. First- and
second-trimester amniocentesis have not been directly
compared in controlled trials.
For low-risk women, the risks
associated with prenatal diagnostic testing (see Adverse Effects of Screening
and Early Detection, below) are generally considered to outweigh the potential
benefits because of the low likelihood of diagnosing a Down syndrome gestation.
If screening tests, such as measurement of maternal serum markers or ultrasound
imaging, can identify women who are at high risk for carrying a Down syndrome
fetus, the relative benefit of prenatal diagnostic testing increases,
potentially justifying the more invasive diagnostic procedures. Reduced levels
of maternal serum a-fetoprotein (MSAFP) and unconjugated
estriol, and elevated levels of human chorionic gonadotropin (hCG), have each been associated with Down syndrome
gestations. Intervention studies of screening have not been carried out with unconjugated estriol alone, while
cohort intervention studies evaluating MSAFP and hCG
have found them to have relatively poor discriminatory power as individual
tests.33-36 Multiple-marker screening uses results from two or three individual
maternal serum marker tests, combined with maternal age, to calculate the risk
of Down syndrome in the current gestation.37,38
Amniocentesis and diagnostic chromosome studies are then offered to women whose
screening test results suggest a high risk of Down syndrome, with high risk
often defined as having the same or greater risk of an affected pregnancy that
a 35-year-old woman has (i.e., 1 in 270).
Six interventional cohort
studies that analyzed low-risk women younger than 35 years,39-41 36 years,42 37 years,43 or 38 years,44 and six that included women of any age desiring screening (90-95% ?5 years),45-50 have
evaluated the proportion of Down syndrome pregnancies identified through
double-marker (hCG and either MSAFP or estriol) or triple-marker screening in the midtrimester compared to the total number of such pregnancies
identified. Interpretation of sensitivity is affected by incomplete
ascertainment of karyotype and incomplete diagnosis
at birth in these studies, although most had active
surveillance systems for Down syndrome cases born to screened women. The reported
sensitivity of multiple-marker screening for Down syndrome ranged from 48 to 91%
(median 64.5%) and the false-positive rate (after revision of dates by ultrasound)
ranged from 3% to 10%. The likelihood of Down syndrome given a positive screening test result
was 1.2-3.8%, depending on the threshold for high risk used to define a positive test
result. In these studies, the threshold chosen ranged from a 1 in 125 to a 1 in 380 chance
of having an affected pregnancy given a positive test result. A young woman
with a prescreen risk of about 1 in 1,000 who tested positive would have a postscreen
risk similar to the risk in women of advanced age who are currently offered
prenatal diagnosis.
Multiple-marker screening has
also been evaluated in women 35 years of age or older, for
whom prenatal diagnosis using amniocentesis or CVS is routinely recommended
because of their increased risk of Down syndrome. Studies suggest that
multiple-marker screening in these women might reduce the need for more
invasive diagnostic tests. In a cohort study of 5,385 women ?5 years of age with no other risk factors, all of whom were undergoing
routine amniocentesis and chromosome studies (thus allowing complete
ascertainment of chromosome abnormalities), estimates of the individual risk of
Down syndrome were calculated based on maternal age in combination with the
results of multiple-marker screening using MSAFP, hCG,
and unconjugated estriol.51 If
amniocentesis were performed only on older women with at least a 1 in 200 risk
of carrying a fetus with Down syndrome based on triple-marker screening, 89% of
affected fetuses would have been detected, 25% of
women with unaffected fetuses would have been identified by screening as
needing amniocentesis. A threshold of 1 in 300
(similar to risk based on age ?5 years
alone) did not add sensitivity but did increase the screen-positive rate to 34%.
Thus, triple-marker screening could have avoided 75% of
amniocenteses in older women, with their attendant risk of fetal loss, at a
cost of missing 11% of cases of Down syndrome. In this study, performing amniocenteses only
on women with postscreen risks of at least 1 in 200 for
Down syndrome would also have detected 47% of fetuses with other autosomal trisomies, 44% of
fetuses with sex aneuploidy, and 11% with
miscellaneous chromosome abnormalities. In previously cited interventional
cohort studies of double- or triple-marker screening that reported separate
results for older women, the Down syndrome detection rate was reported as 80-100% for
women ?5 years43,46,47,50 and 100% for women ?6 years,42,45 with false-positive screening results of 19-27%.
Incomplete case ascertainment was possible, however, since screen-negative
women rarely had diagnostic chromosome studies.
Although no controlled trials
have directly compared double-marker to triple-marker screening, several cohort
studies of triple-marker screening have reported the detection rates for
double-marker screening with hCG
and MSAFP only. Three markers appear to be somewhat more sensitive than two for
detection of Down syndrome; the net difference in sensitivity ranged from - 2 to +18% in
these studies, depending on the false-positive rate and risk cut-off used.43,48,50,51
Ultrasonography is another potential screening test for Down syndrome. Abnormalities
associated with Down syndrome (including intrauterine growth retardation,
cardiac anomalies, hydrops, duodenal and esophageal atresia) and differences in long-bone length and nuchal fold thickness between Down syndrome and normal
pregnancies observable on midtrimester ultrasound
have been reviewed.52 In prospective cohort studies of midtrimester
ultrasound screening in high-risk women who were undergoing amniocenteses for
chromosome studies, nuchal fold thickening identified
75% of Down syndrome fetuses; shortened humerus or
femur length detected 31%; and an index based on thickened nuchal fold,
major structural defect, and certain other abnormalities identified 69%.53-55 The
likelihood of Down syndrome given a positive result was 7-25% in
these high-risk samples, but would be substantially lower in low-risk women. No
published cohort studies have evaluated the accuracy of ultrasound screening
for detection of chromosome abnormalities in low-risk women, nor have
interventional cohort studies evaluated its efficacy as a screening tool in
high-risk women. The use of ultrasound as a screening test for Down syndrome is
limited by the technical difficulty of producing a reliable sonographic
image of critical fetal structures.56,57
Incorrect positioning of the transducer, for example, can produce artifactual images resembling a thickened nuchal skin fold in a normal fetus.58 Sonographic indices are therefore subject to considerable
variation. Imaging techniques require further standardization before routine
screening by ultrasound for Down syndrome can be considered for the general
population.56,59,60 In addition, results
obtained by well-trained and well-equipped operators in a research context may
not generalize to widespread use. In a multicenter
cohort study in high-risk women that involved a large number of ultrasonographers of varying ability, the sensitivity of nuchal fold thickening for Down syndrome was only 38%.59 The
false-psitive rate in this study was 8.5%, many
times higher than that reported in studies involving expert ultrasonographers.55,61
Effectiveness of Early
Detection
The detection of Down syndrome and other chromosome anomalies in utero provides as its principal benefit the opportunity to
inform prospective parents of the likelihood of giving birth to an affected
child. Parents may be counseled about the consequences of the abnormality and
can make more informed decisions about optimal care for their newborn or about
elective abortion. No controlled trials have been performed to assess clinical
outcomes for those using screening or prenatal diagnosis for Down syndrome
compared to those who do not. Therefore, the usefulness of this information
depends to a large extent on the personal preferences and abilities of the
parents.62 Whether or not parents choose to use prenatal screening or diagnosis is
related both to their views on the acceptability of induced abortion and their
perceived risk of the fetus being abnormal.63 The
perception of the harm or nature of the disability may play a greater role in
the decision than the actual probability of its occurrence.64-67
Induced abortion is currently
sought by the majority of women whose prenatal diagnostic studies (i.e., karyotyping) reveal fetuses with Down syndrome.33-35,39,40,45,48,68 Estimates of the reduction in birth prevalence of Down syndrome
associated with offering prenatal diagnosis to women 35 years
and older range from 7.3% to 29% in the U.S. and other developed countries.2,69-73 The
effect of this approach on the total number of Down syndrome births is limited
because older women have low birth rates and therefore account for a relatively
small proportion of affected pregnancies despite their exponentially increased
risk for having an affected pregnancy.74 Limited data are available to
estimate the impact of serum-marker screening in younger women on Down syndrome
birth prevalence. In England and Wales, the proportion of all cytogenetically
diagnosed Down syndrome cases detected prenatally
(thus potentially preventable) increased from 31% to 46% after
the introduction of screening by maternal serum analysis and ultrasound for
low-risk women.68 In cohort studies evaluating double- or triple-marker screening, when the
proportions of screen-positive women who decided not to undergo amniocentesis
or induced abortion were taken into account, the proportion of Down syndrome
births to screened women that were actually prevented ranged from 36% to 62%.39,40,45,48 Up to 25% of
screen-positive women declined prenatal diagnosis by amniocentesis in these
studies. The effectiveness of screening in preventing Down syndrome births may
be further reduced by incomplete uptake of screening. In antenatal screening
programs in which double- or triple-marker screening was offered to all women
and amniocentesis or CVS was offered to women over 35 years
of age, nearly 60% of all Down syndrome births were potentially preventable, the remainder
either being missed by screening (14-23%) or
occurring in women who were not screened (17-27%).47,49 Neither study evaluated
acceptance of induced abortion, however. In another population, offering ouble-marker screening to all women prevented 59% of
all Down syndrome births.45 This
population had high rates of screening (89%), largely due to the fact
that pregnant women had to specifically ask to be excluded. There was also high
acceptance of amniocentesis in screen-positive women (89%), and
of induced abortion of cytogenetically confirmed cases (91%). The
birth prevalence of Down syndrome decreased from approximately 1.1/1,000 to 0.4/1,000 after initiation of prenatal screening in this population.
Other potential effects of
prenatal detection of Down syndrome have not been adequately explored. In
families at high risk of Down syndrome births, such as those with advanced
maternal age, a previous affected pregnancy, or known carriage of
translocations, the availability of prenatal diagnosis may reduce the induced
abortion rate by identifying normal pregnancies that might otherwise be
electively aborted. This benefit has been reported with screening for cystic
fibrosis,75 but it has not been
evaluated for Down syndrome. The diagnosis of a chromosome abnormality may
spare unsuspecting parents some of the trauma associated with delivering an
abnormal infant, and may help parents to prepare emotionally. Studies
evaluating these potential psychological benefits have not been reported,
however. Prenatal diagnosis may also enable clinicians to better prepare for
the delivery and care of the baby. Studies are lacking regarding the impact of
these measures on neonatal morbidity and mortality.
An indirect benefit of testing
to detect Down syndrome is the discovery during testing of abnormalities other
than the target condition. Chromosome studies on specimens obtained by
amniocentesis or CVS will detect other abnormalities besides Down syndrome. Autosomal trisomies other than
Down syndrome are usually spontaneously aborted, so the principal benefit of
screening may be avoidance of late fetal death.76 The
health consequences of sex aneuploidy are less
significant than trisomies, but about half such
pregnancies are nevertheless electively aborted when discovered prenatally.77,78 Serum
marker screening for Down syndrome will also identify some patients carrying
fetuses with other chromosome abnormalities (e.g., Turner syndrome, trisomy-13 or -18);
sensitivity is low,51 however, because some of these abnormalities have different effects on
serum markers than does Down syndrome, and require different risk thresholds.50,79
Ultrasound screening for Down syndrome leads to a more accurate assessment of
gestational age in women with uncertain dates, and some studies suggest that
acting on this information may reduce the likelihood of induced labor for
erroneously diagnosed postterm pregnancy (see Chapter
36). Multiple gestations and major congenital anomalies, such as
diaphragmatic hernia, gastroschisis, nonimmune fetal hydrops, and
obstructive uropathy, may also be detected by
ultrasound. These discoveries permit antenatal treatment as well as delivery
and neonatal care planning. Controlled trials proving that early detection by
ultrasound of multiple gestations or congenital anomalies improves outcome have
not been published, however (see Chapter 36).
Adverse
Effects of Screening and Early Detection. The
most important risks of early detection of Down syndrome include those to the
fetus from amniocentesis and CVS performed as a primary or follow-up diagnostic
test, the psychological effects of a positive test on the parents, and the
complications resulting from induced abortion. The risks of amniocentesis
include rare puncture of the fetus, bleeding, infection, and possibly
isosensitization.80,81 The
procedure-related rate of fetal loss with current technique appears to be about
0.5-0.8%.16,17,29 The best evidence on amniocentesis risks comes from a randomized
controlled trial of screening,16 which reported a
procedure-related risk of fetal loss of 0.8% of pregnancies. This may
nevertheless overestimate current rates of loss as techniques have improved. In
a more recent series of patients undergoing amniocentesis as part of a clinical
trial, the risk of fetal loss was 0.04%.22 In a
randomized controlled trial, neonatal respiratory distress syndrome and
neonatal pneumonia were more frequent after amniocentesis, independent of birth
weight and gestational age; the additional risk was about 1%.16 A
similar trend was seen in the Medical Research Council study,18 but has not been confirmed in other studies. Infection has not been
identified as a significant problem in any large studies. No clinically
important effects on development, behavior, or physical status were identified
in 4-year-old children whose mothers had undergone midtrimester
amniocentesis.83 Case series of women undergoing first-trimester amniocentesis suggest a
procedure-related fetal loss rate of 3-7%.84-87 In a
randomized controlled trial, the total fetal loss rate with early amniocentesis
was significantly higher than with CVS (5.9 vs. 1.2%).32
Several randomized controlled
trials comparing amniocentesis and CVS have reported significantly higher fetal
loss rates with CVS (1.0-1.5%) when compared with second-trimester amniocentesis.20-22
Inexperience and the use of transcervical CVS appear
related to a greater risk of fetal loss, although at least one trial found no
significant difference in fetal loss rates between transcervical
and transabdominal CVS (2.5% vs. 2.3%).31 An
increased risk of transverse limb reduction anomalies in infants born after CVS
has been reported in case-control and case-series studies.88-93b
Conflicting evidence from cohort studies may relate to varying methods of case
ascertainment or classification.94-99a
Decreasing risk and a trend from proximal to distal limb damage with increasing
gestational age at CVS provide biologic plausibility for a true association
with limb reduction defects.93,99b
Current estimates for the overall risk of transverse limb deficiency from CVS
range from 0.03% to 0.10% of procedures.99a Severe maternal complications from CVS are rarely reported, but the
Canadian Collaborative Study suggested a higher risk of bleeding requiring
intervention for women undergoing CVS compared to amniocentesis.22 None
of the CVS trials has reported increased risks of birth defects or major infant
health problems, but sample size is inadequate in these trials to rule out rare
adverse effects.
A positive screening test
result can produce a harmful psychological effect on parents. This is
especially important because the large majority of positive screening tests occur
in normal pregnancies. Adverse psychological effects of screening tests include
the fear of discovering an abnormal pregnancy as well as anxiety over possible
complications from diagnostic and therapeutic procedures. Women who have been
identified as being at high risk because of a positive serum-marker screening
test may have greater distress than women who are identified as high risk
because of advanced age.100,101 Distress is reduced following a diagnostic procedure confirming a normal
pregnancy, but some anxiety related to the false-positive screening test may
persist.102,103 Most women screened will have normal results, however, and this may have
psychological benefits for the reassured parents.
The potential complications of
induced abortion must also be considered, since this is the outcome of the
majority of positive diagnostic test results. Morbidity from first-trimester
induced abortion, including infection, hemorrhage, and injury, occurs in 2-3% of
procedures, but serious complications are rare; in one series of 170,000 cases, 0.07% required hospitalization and none resulted in death.104-107
Complication rates, including maternal case-fatality rates, are higher with
second-trimester abortions, but remain uncommon.108-110 The
case-fatality rate from legally induced abortion, 0.4/100,000 procedures, is substantially lower than the risk of pregnancy-related
death, which is 8-9/100,000 live births.108,109,111,112 The most serious consequence of false-positive test results, the induced
abortion of a normal pregnancy, was not reported in any of the trials, and
appears to be rare with current techniques. The likelihood of diagnostic error
is slightly higher with CVS than with amniocentesis, but the risk of induced
abortion as a consequence has not been fully evaluated.
Recommendations of Other Groups
Most organizations recommend offering amniocentesis or CVS for prenatal
diagnosis to all pregnant women who are aged 35 years
and older or otherwise at high risk for chromosome abnormalities.113-115 The Canadian
Task Force on the Periodic Health Examination concluded that there is fair
evidence to offer second-trimester triple-marker screening to all pregnant
women less than 35 years of age, and as an alternative to prenatal diagnosis by karyotyping in women 35 years and older; such offering
should be accompanied by education on its limited efficacy, as well as on the
risks of second-trimester diagnosis and abortion, and on the psychological
implications of screening and of a Down syndrome birth.114
Offering multiple-marker screening between 15 and 18 weeks
of gestation to low-risk women under 35 years of age to assess Down
syndrome risk is also recommended by the American College of Obstetricians and
Gynecologists (ACOG) and the American College of Medical Genetics (ACMG);
neither group recommends a specific multiple-marker protocol.115,116
Neither ACOG nor ACMG recommends prenatal cytogenic
screening by multiple-marker testing in women 35 years
and older; ACOG recommends that multiple-marker testing may be offered as an
option for those women who do not accept the risk of amniocentesis or who wish
to have this additional information prior to making a decision. No
organizations currently recommend routine screening for Down syndrome by
ultrasound. ACOG117 and a National Institutes of Health consensus development conference118 have
recommended that ultrasound imaging be performed during pregnancy only in
response to a specific medical indication.
Discussion
Prenatal diagnostic testing is accurate and reliable for
detecting Down syndrome, but it is associated with a procedure-related fetal
loss risk of about 0.5% for second-trimester amniocentesis and 1-1.5% for
CVS, and a measurable risk of transverse fetal limb deficiency after CVS. The
currently accepted medical practice of routinely offering amniocentesis or CVS
for prenatal diagnosis to pregnant women aged 35 years
and older or otherwise at high risk is based on the mother's increased risk of
having a fetus with a chromosome abnormality balanced against the risk of fetal
loss associated with these procedures, and therefore includes an element of
judgment. It can be predicted from available data (odds of Down syndrome during
the second trimester) that a program offering amniocentesis to all pregnant
women at age 35 has the potential of exposing 200-300 normal
fetuses to this procedure for every case detected.10 With
an estimated procedure-related fetal loss rate of 0.5%, one
normal fetus would be lost by amniocentesis for every one to two chromosome
anomalies detected in such women. For CVS, the number of normal fetuses lost
per case detected would be higher, and for first-trimester amniocentesis, it
may be higher still. The older the maternal age, the more
favorable the ratio of affected fetuses to fetal loss. Most women who
request such testing and receive a diagnosis of a Down syndrome pregnancy
choose to abort the pregnancy, resulting in a measurable reduction in Down
syndrome births. There is little good evidence of the effect on personal and
family outcomes, however, or on the balance of risks and benefits for the group
as a whole. Nevertheless, those women at high risk who desire prenatal
diagnosis of Down syndrome may benefit substantially from it. Thus, there is
fair evidence to support offering prenatal diagnosis to high-risk pregnant
women who are identified by age, history, or screening tests when a
comprehensive prenatal diagnosis program that includes education,
interpretation, and follow-up is avaiable.
In low-risk pregnant women,
maternal serum multiple-marker screening in the second trimester can detect
nearly two thirds of Down syndrome fetuses, but it will result in a large
number of young women being offered amniocentesis who would not otherwise be
subjected to its risks. The ratio of affected fetuses detected to
procedure-related fetal loss in women with positive multiple-marker screening
would be similar to or more favorable than that of women 35 years
and older. The risk of fetal loss may be acceptable to parents with strong
fears of having an affected child.64,119-121 There
is also evidence that multiple-marker screening in women 35 years
and older can detect 80% or more of Down syndrome pregnancies while allowing the majority of such
women to avoid the risks associated with invasive diagnostic testing.
Multiple-marker screening is not supported by the same strength of evidence as
is amniocentesis or CVS, however. Potential problems include the reduced
sensitivity for Down syndrome and other chromosome abnormalities, the large
proportion of false-positive tests, and the substantial number of women who
refuse or do not receive follow-up amniocentesis and chromosome studies. This
is of particular concern if such screening is offered to women 35 years
and older who might otherwise receive amniocentesis or CVS. Nevertheless, in
some older women, particularly those who may have had difficulty conceiving or
carrying a pregnancy, the reduced likelihood of amniocentesis or CVS and
consequent risk of fetal loss or injury may outweigh the reduced sensitivity of
multiple-marker screening. There is therefore fair evidence to support offering
multiple-marker screening to pregnant women of all ages when a comprehensive
prenatal diagnosis program is available that includes education,
interpretation, and follow-up.
There is a lack of sound
evidence to support the use of individual maternal serum markers to screen for
Down syndrome, and currently available evidence suggests that sensitivity is
substantially lower than with multiple-marker screening. Similarly, ultrasonography has not been adequately evaluated as a
routine screening test for Down syndrome, and there are important concerns
about the measurement reliability and generalizability
of this technology to widespread use. Since there is evidence supporting the
effectiveness of other screening and diagnostic methods, neither individual
serum markers nor ultrasonography can be recommended
as screening tests for Down syndrome outside clinical trials.
Identification and selective
abortion of Down syndrome pregnancies raises important ethical concerns, a full
discussion of which is beyond the scope of this chapter. These concerns include
the implicit message that Down syndrome is an undesirable state, the
interpretation of induced abortion in eugenic terms by some persons, and
societal and economic pressures that may stigmatize families with a Down
syndrome member. Attitudes held by both physicians and by society toward
individuals with Down syndrome have changed over time, and various Down
syndrome associations now offer support for families and individuals with Down
syndrome, promote their participation in society, and seek respect for them.122,123 These
issues highlight the importance of offering screening and prenatal diagnosis of
Down syndrome in a value-sensitive fashion with emphasis on reliable
information about Down syndrome itself as well as about the potential risks and
benefits of screening procedures.
In these recommendations,
primary consideration has been given to the prenatal detection of Down syndrome.
Other chromosome anomalies (e.g., Turner syndrome, trisomy-18) are
often detected during prenatal screening and diagnosis and many may consider
their detection important. There are few studies directly addressing screening
for these conditions, however, and screening protocols have not been
sufficiently evaluated to warrant review at this point.
CLINICAL INTERVENTION
The offering of amniocentesis or CVS for chromosome studies to pregnant women
aged 35 years and older and to those at high risk of Down syndrome for other
reasons (e.g., previous affected pregnancy, known carriage of a chromosome
rearrangement associated with Down syndrome) is recommended ("B"
recommendation). In some circumstances, depending on resources, preferences,
and other factors, the selection of a different age threshold for offering
prenatal diagnosis may be considered. Counseling before the procedure should
include a comparison of the risks to the fetus from the procedure and the
probability of a chromosome defect given the patient's age or other risk
factors, as well as a full discussion of the potential outcomes associated with
delivering a child with Down syndrome and of aborting a Down syndrome fetus.
The offering of screening for
Down syndrome by maternal serum multiple-marker testing at 15- 18 weeks
of gestation is recommended for all pregnant women who have access to
counseling and follow-up services, skilled high-resolution ultrasound and
amniocentesis capabilities, and reliable, standardized laboratories
("B" recommendation). There is currently insufficient evidence to
recommend a specific multiple-marker screening protocol. Counseling regarding
screening should include information on the procedure itself, the likelihood of
follow-up testing with amniocentesis and its associated risks, as well as a
full discussion of the potential outcomes associated with delivering a child
with Down syndrome and of aborting a Down syndrome fetus. Women with a positive
screen should receive detailed information comparing the increased risk of trisomy and the risks of fetal loss from amniocentesis. For
women aged 35 years and older, the choice of serum multiple-marker screening versus
amniocentesis or CVS for chromosome studies depends on patient preferences and
therefore requires a detailed discussion of the potential risks and benefits of
each procedure. In particular, the patient should understand the reduced
sensitivity of multiple-marker screening for Down syndrome and for other
chromosome abnormalities compared to prenatal diagnosis by chromosome studies,
and the increased risk of fetal loss or injury with amniocentesis and CVS.
There is currently insufficient
evidence to recommend for or against routine ultrasound examination or the use of
individual maternal serum markers in pregnant women as screening tests for Down
syndrome ("C" recommendation). Recommendations against these tests
may be made on other grounds, however, including the availability of other
screening tests of proven effectiveness.