privileged to work with many genetic counselors in theirpractices. This article was in no way intended to diminishthe value added to patient care by the skill and supportprovided by genetic counselors. This genetic counselingis the gold standard by which all other methods of patientgenetic education and counseling will be judged. Mostobstetric patients, however, will not have the opportunityor indications for formal genetic counseling in their preg-nancy; this does not mean, however, that they will nothave questions that may have a genetic focus.

In the practice of prenatal screening for cystic fibrosis,many patients receive inadequate explanations for the in-dications and interpretation of screening and find them-selves devastated by the identification of an unsuspectedmutation. This article addressed 1modality for improvingthis prescreening education, recognizing that the largenumbers of obstetric patients should be provided morethan a brief question of preference for screening, althoughthey may not be able to support, either in terms of timeand/or cost, a uniform referral for genetic counseling. Ifall obstetric practices had a genetic counselor in houseand if all insurance programs adequately reimbursed ge-netic counselors for their services, uniform genetic coun-seling of prenatal patients would undoubtedly provideadded value to obstetrics care.2,3

Such circumstances, however, are not universal. AsMs. Ormand points out, there are approximately 2000trained genetic counselors, 1000 clinical geneticists,and 100 genetic nurse specialists in this country. Givena birth rate of approximately 4 million liveborn infantsper year in the United States, these 3000 professionals

would be expected to each see more than 1200patients/year to provide counseling to all obstetricspatients. Although this would be very stimulating tothe practice of genetic medicine, many physicians andcounselors do cluster in major medical centers andhave differing focuses of practice from prenatal care.In the state of Mississippi, where the study in questionwas conducted, there are less than 5 genetic counselorsin the whole state. Thus, genetic education must be pro-vided by someone other than a counselor. The authorscontinue to believe that adequate genetic educationcan be provided by multiple means, including audio-visual approaches, recognizing that formal genetic coun-seling will be a necessity for those couples identified withmutations or at risk for other genetic diseases.

Melissa H. Fries, Col USAF MC**National Naval Medical Center

Bethesda, MD 20814

References

1. Fries MH, Bashford M, Nunes M. Implementing prenatal screening

for cystic fibrosis in routine obstetric practice. Am J Obstet Gynecol

2005;192:527-34.

2. Bernhardt BA, Biesecker BB, Mastromarino CL. Goals, benefits,

and outcomes of genetic counseling: client and genetic counselor

assessment. Am J Med Genet 2000;94:189-97.

3. Koscica KL, Canterino JC, Harrigan JT, Dalaya T, Ananth CV,

Vintzileos AM. Assessing genetic risk: comparison between the re-

ferring obstetrician and genetic counselor. Am J Obstet Gynecol

2001;185:1032-4.

0002-9378/$ - see front matter � 2006 Mosby, Inc. All rights reserved.

doi:10.1016/j.ajog.2005.07.025

Letters to the Editors 905

Fetal RhD genotyping by maternal serum analysis:A two-year experience

To the Editors: I read with great interest the article byGautier et al.1 I have a few comments.

1. We are not told the gravidity or pregnancy intervalfor the study patients. It has been well establishedthat fetal cells may persist in maternal blood andtissues for some time following pregnancy.2 It istherefore critical to establish that the assay resultsdo not reflect previous pregnancies.

2. We are not told the ABO compatibility of themother-fetus pairs. It has been reported thatABO-compatible mother-fetus pairs are at increasedrisk for Rh isoimmunization. This increase is

presumably secondary to an increase in the survivalof fetal cells in the maternal circulation. It is there-fore conceivable that the assay sensitivity may be af-fected by the ABO status of the mother-fetus pairs.

3. Determination of the fetal Rh status via chorionicvillus sampling or amniocentesis followed by poly-merase chain reaction Rh genotyping is associatedwith a 1% to 3.9% false-negative rate (an Rhpositive fetus is identified as Rhe).3 Whereas the re-sults presented by Gautier et al are encouraging, astudy population several times larger would be re-quired to determine whether a similar false-negativerate also plagues this assay system.

906 Letters to the Editors

4. Gautier et al maintain that the routine use of thisassay would decrease the number of rhogam dosesadministered. Although this is true, this benefit mustbe weighed against the cost of the assay, theprevalence of Rh homo- and heterozygosity in thepopulation, and the current and future pregnancyimplications of withholding Rhogam in a pregnancywith false-negative results.

Dr Henry Roque**University of Connecticut

Obstetrics and Gynecology Divisionof Maternal-Fetal Medicine, CG-214

0002-9378/$ - see front matter � 2006 Mosby, Inc. All rights reserved.

doi:10.1016/j.ajog.2005.07.023

Reply

To the Editors: Thank you for giving us the opportunityto respond to the letter from Dr. Roque with regard toour recent paper on the noninvasive approach for fetalRhD genotyping using maternal blood. We agree thatthe risk for RhD immunization is influenced by ABOgroup compatibility between the fetus and the motherand that fetal cells from previous pregnancies may per-sist for a long time after delivery. However, it is nowwell demonstrated that, if persisting in maternal blood,fetal cells contribute only to a minor part of cell-free fe-tal DNA that circulates in plasma and serum. As a con-sequence, even if they are present, fetal cells have noinfluence on the result obtained by cell-free fetal DNAanalysis because of their extremely low number. Thehigh level of accuracy obtained by many groups foreither fetal RhD genotyping or fetal sexing supportsthis idea.1 Furthermore, it has been demonstrated thatcell-free fetal DNA does not persist in plasma or serumafter delivery, and therefore, its analysis cannot reflectthe status of a previous pregnancy.2,3

The second part of Dr. Roque’s comments is highly in-teresting because the possibility of false-negative results issurely themain concern of the project. Because of the pos-sibility of a negativemedical impact (alloimmunization ofpregnant woman) and its cost, we agree that such a riskmust bewell evaluated. For this reason, large-scale studiesare in progress by our group as well as others around theworld. However, one can be optimistic because the rate offalse-negative results could be easily and dramatically re-duced by either defining the appropriate timing for sam-pling during pregnancy (not too early) and/or repeatingthe analysis (ie, later in pregnancy). Developing simple

0002-9378/$ - see front matter � 2006 Mosby, Inc. All rights reserved.

doi:10.1016/j.ajog.2005.07.024

263 Farmington AvenueFarmington, CT 06030

E-mail: roque@uchc.edu

References

1. Gautier E, Benachi A, Giovangrandi Y, Ernault P, Olivi M,

Gaillon T, et al. Fetal RhD genotyping by maternal serum analysis:

a two-year experience. Am J Obstet Gynecol 2005;192:666-9.

2. Khosrotehrani K, Bianchi DW. Multi-lineage potential of fetal cells

in maternal tissue: a legacy in reverse. J Cell Sci 2005;118(Pt 8):

1559-63.

3. Van den Veyver IB, Moise KJ Jr. Fetal RhD typing by polymerase

chain reaction in pregnancies complicated by rhesus alloimmuniza-

tion. Obstet Gynecol 1996;88:1061-7.

but robust and reliable assays, educating clinical labora-tories, and introducing proficiency testing might help toachieve this goal.

Studies are currently in progress with regard to thefinancial impact of establishing a systematic policy ofnoninvasive fetal RhD genotyping for RhD negativepregnant women. This policy might imply additionalcost, but this should be weighted against the risk of ad-ministration of a blood-derivative product to a pregnantwomen in case of a RhD-negative fetus.

Jean-Marc Costa*Evelyne Gautier*

*Centre de Diagnostic PrenatalAmerican Hospital of Paris

Neuilly, France

Alexandra Benachi**Maternite

Hopital Necker-Enfants MaladesParis, France

References

1. Daniels G, Finning K, Martin P, Soothill P. Fetal blood group gen-

otyping from DNA from maternal plasma: an important advance in

the management and prevention of haemolytic disease of the fetus

and newborn. Vox Sanguinis 2004;87:225-32.

2. Smid M, Galbiati S, Vassallo A, Gambini D, Ferrari A, Viora E,

et al. No evidence of fetal DNA persistence in maternal plasma after

pregnancy. Hum Genet 2003;112:617-8.

3. Benachi A, Steffann J, Gautier E, Ernault P, Olivi M, Dumez Y,

et al. Fetal DNA in maternal serum: does it persist after pregnancy?

Hum Genet 2003;113:76-9.