BEST PRACTICE GUIDELINES - Prenatal screening & cord blood banking

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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