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Best practices in: prenatal
screening & cord blood banking
OB/GYN News, Jan, 2011
by
Joanne Stone
INTRODUCTION
Recent developments in prenatal testing
and umbilical cord blood (UCB) banking are providing
obstetrician/gynecologists (Ob/Gyns) with the opportunity to
help expectant parents anticipate potential health issues
and protect the health of their families during the prenatal
period and beyond. These developments include improved
detection of possible fetal chromosomal abnormalities during
the first trimester and increased use of UCB banking.
Many expectant parents may not be aware
of these technologies--others may be confused or
inadequately informed about them and how to navigate the
decision-making process. By being fully conversant with
these new developments, the Ob/Gyn can help expectant
parents make educated decisions.
Screening for Fetal Chromosomal
Abnormalities
Based on improvements in the sensitivity
and specificity of early screening techniques, the American
College of Obstetrics and Gynecology (ACOG) now recommends
all women be offered screening for fetal aneuploidy. (1)
Although the relative risk of Down syndrome (DS) increases
with maternal age, the incidence of affected pregnancies is
actually greatest among women younger than age 35, because
of their higher pregnancy rate. In the United States, an
estimated 80% of DS cases involve mothers under age 35.(2)
Therefore, screening is an important component of prenatal
care regardless of maternal age.
Even when
pregnancy termination is not an option for expectant
parents, early identification of fetal abnormalities
maximizes the time available for planning and preparation.
Frequent complications of DS include congenital heart
defects, leukemia, and premature dementia; preparation for a
DS birth may involve a cardiology consult, birth in a NICU-equipped
hospital, and financial and health insurance planning.
Ultrasonographic and serum markers now make it possible to
identify potential fetal chromosomal abnormalities with
detection rates > 90% at low false-positive rates (5%) by
the second trimester. (1),(3) These techniques, in turn,
make it possible to more accurately target specific
pregnancies for invasive diagnostic procedures such as
chorionic villus sampling (CVS) or amniocentesis, minimizing
the risk of procedure-associated loss of normal fetuses. (1)
However,
prospective parents must understand that optimizing the
sensitivity and usefulness of these markers requires that
screening be initiated early, during the first trimester.
Protocols that incorporate first trimester screening provide
estimated DS detection rates that are approximately 15%
higher than the best combination of second trimester--only
screens. (3),(4)
Nuchal
translucency (NT), the most reliable ultrasonographic marker
for chromosomal abnormalities, can only be used during the
first trimester. The addition of first trimester serum
markers improves detection sensitivity over NT alone by
~15%.(1), (3) The most useful first trimester serum markers
include pregnancy-associated plasma protein A (PAPP-A) and
free beta human chorionic gonadotropin (hCG) or total hCG,
for which results are reported as multiples of the median
(MoM). There is evidence that free beta hCG demonstrates
greater MoM deviation in DS cases than total hCG, which may
result in higher DS detection rates during the first
trimester.(5) The power of combining NT and serum markers
with regard to first trimester sensitivity for DS and other
chromosomal abnormalities was demonstrated by a study
conducted in a noninvestigational setting, in which the
combination of NT, free beta hCG, and PAPP-A demonstrated a
91% DS detection rare at a 5% false-positive rate. (6)
During the
second trimester, alpha-fetoprotein (AFP), unconjugated
estriol, and inhibin-A become important markers for
aneuploidy and open neural tube defects (ONTDs).(1)
Sequential screening protocols (in which second trimester
testing is combined with results of first trimester tests)
result in the highest reported detection rates for
aneuploidy (94% to 95%) and ONTDs. (3),(7),(8)
A positive
screening result is usually followed by genetic counseling
for the prospective parents, to discuss the risk associated
with one or more positive results and the need for
additional testing. The range of additional testing options
is not confined to CVS and amniocentesis; ultrasound or
other evaluations may help clarify ambiguous screening
results (eg, increased NT with normal chromosomal analysis)
and help parents better prepare for postnatal care.
Depending on family history, other genetic screens (such as
microdeletion analysis) may also be useful.
In this
context, the ability to provide a detailed risk evaluation
immediately after screening tests are completed can help to
avoid the need for call-backs and new appointment
scheduling; it can also minimize anxiety that prospective
parents may experience waiting for results and maximize
their time to consider their options. For example, NTD Labs
provides Instant Risk Assessment (IRA), which is based on
analysis of a dried blood sample that may be collected as
early as 9 weeks, before the ultrasonographic NT scan. IRA
enables Ob/Gyns to provide a complete aneuploidy risk
assessment to prospective parents at the conclusion of
ultrasound testing, facilitating early planning and
scheduling of additional diagnostic procedures.
UCB
Banking
Another
opportunity for Ob/Gyns to help expectant parents plan for
potential health crises is through education about UCB
banking. UCB contains both hematopoietic stem cells (HSCs)
and pluripotent stem cells. Technological advances now
permit the cryopreservation and banking of UCB, with high
rates of functional recovery, for at least 15 years and
perhaps indefinitely. (9) This capability means that banked
UCB may be available as a tool for various therapies
throughout the lifespan of a neonate born today.
The most
widespread current use of banked UCB is as a source of FISCs
for hematopoietic stem cell transplantation (HSCT) in the
treatment of malignant and nonmalignant diseases. (10), (11)
In this context, UCB can provide a superior alternative to
allogeneic bone marrow transplant: in one study, the
incidence of graft-versus-host disease was significantly
lower among recipients of UCB from human leukocyte antigen
(HLA)-matched siblings than among recipients of bone marrow
transplants from HLA-matched siblings. (12) Although some
estimate the probability of using cord blood at 1 in 2700,
recent analyses suggest that as many as 1 in 217 people may
require HSCT by age 70. (13),(14)
The therapeutic
potential for UCB is likely to expand dramatically in the
coming decades. UCB-derived stem cells are under intense
investigation as therapy for a wide (and steadily
increasing) range of hematologic and nonhematologic
disorders. In contrast to transplantation therapy today,
many of these emerging therapies will require the use of
one's own UCB. Early clinical trials are proceeding, with
promising results, in type I diabetes and cerebral palsy.
(15), (16) Other potential uses under preclinical
investigation include cardiovascular disease, multiple
sclerosis, stroke, amyotrophic lateral sclerosis, and bone
regeneration.(16) More than 50 clinical trials involving the
use of UCB are currently listed on the National Institutes
of Health clinical trials Web site. (17)
Most patients
are poorly informed with respect to UCB and UCB banking
options. (18),(19) As recognized in a 2008 update of a 1997
ACOG committee opinion, Ob/Gyns are a vital source of
patient-directed information on UCB banking and should be
prepared to discuss banking options with any patients who
express an interest.(14) It should be stressed that donation
of UCB is a "one-shot" opportunity that in later life may
provide therapeutic benefits, many of which are still being
explored.
The most
important distinction Ob/Gyns need to make when discussing
UCB banking options is the difference between public and
family (private) UCB banking. Public UCB banks operate much
like blood banks, providing patients who need HSCT with a
potential source of donor cells. However, donors cannot be
guaranteed subsequent access to their own or a relative's
UCB, in contrast to family banking, where such access is
guaranteed.
For many
patients, family banking may be the preferred option.
Transplant patients who have access to stored UCB stem cells
from a related source have an optimal chance of obtaining a
suitable matching donor source. (12),(16) In addition, the
1-year survival rate following UCB stem cell transplants was
increased by more than twofold when related donors rather
than unrelated donors were the source of UCB.-" Although
there is a financial commitment associated with family UCB
banking, Ob/Gyns should present all options to prospective
parents (even when their socioeconomic situation may be a
concern) to preserve the patients' ability to make their own
proactive decisions.
In helping prospective parents select a family banking
option, the Ob/Gyn should consider the stability, history,
and technical capability of private facilities. An example
of a trusted UCB banking facility is ViaCord, which has
worked with Ob/Gyns for more than 15 years and currently
stores UCB from over 200,000 families nationwide. In
conjunction with its parent company, PerkinElmer, a $2
billion global company, ViaCord maintains a research
institute committed to finding new uses for UCB stem cells
and works closely with outside researchers investigating
such uses. In addition, ViaCord actively facilitates
enrollment of relevant clients into early clinical trials
with UCB, such as a Duke University trial for children with
cerebral palsy; preliminary anecdotal results suggest
promising recovery of movement and cognitive functioning in
such children following autologous infusion of their own
stored cord blood.
Conclusions
The technologies described here are empowering prospective
parents with a range of choices to help protect the health
of their families. New prenatal screening techniques enable
very early detection of possible chromosomal abnormalities,
maximizing the time available for decision-making and
preparation for possible health-related complications. The
ability to bank UCB is already paying dividends with respect
to transplantation-based therapy and is likely to provide
many additional therapeutic opportunities in years to come.
Ob/Gyns should continue to follow these developments to
ensure they provide the highest quality of care and
information to their current and future patients.
References
(1.) ACOG Committee on Practice Bulletins. Obstet Gynecol.
2007;109(1)217-227.
(2.) Palomaki GE, Haddow JE. Am J obstet Gynecol. 1987;
156(2):460-463.
(3.) Malone FD, et al. N Engl J Med. 2005;353(19):2001-2011.
(4.) Canick JA. 0BG Management (online). 2005; 17(12).
(5.) Data on file. NTD Labs.
(6.) Perni SC, et al. Am J Obstet Gynecol. 2006; 194(1):
127-130
(7.) Cuckle. H, et al. Semin Perinatol. 2005;29(4):252-257
(8.) Spencer K, Nicolaides KH. Prenat Diagn.
2002;22(10):877-879.
(9.) Broxmeyer HE, et al. Proc Natl Acad Sci USA.
2003;100(2):645-650.
(10.) Rocha V, et al. Rev Invest Clin. 2005;57(2):314-323.
(11.) Rubinstein P. Hum Immunol. 2006;67(6): 398-404.
(12.) Rocha V, et al. N Engl J Med. 2000;342(25): 1846-1854.
(13.) Nietfeld JJ, et al. Biol Blood Marrow Transplant.
2008;l4(3):316-322.
(14.) Committees on Obstetric Practice and Genetics. Obstet
Gynecol. 2008; 111 (2 Pt l):475-477.
(15.) Haller MJ, et al. Exp Hemalol. 2008;36(6):710-715.
(16.) Einstein F, Merkatz I. Contemporary OB/GYN. 2008;
October (suppl):l-15.
(17.) http://clinicaltrials.gov. Accessed October 29, 2009.
(18.) Fox NS, et al J Perinal Med. 2007;35(4):314-321.
(19.) Perlow JH. J Repord Med. 2006;51(8):642-648.
(20.) Gluckman E, et al. N Engl J Med. 1997;337(6):373-381.
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This supplement was produced by International Medical News
Group, a division of Elsevier Medical Information, LLC.
Neither the editor of Ob.Gyn. News, the Editorial Advisory
Board, nor the reporting staff contributed to its content.
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