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Letters to the Editor |
Prenatal Diagnostic Center, Guangzhou Maternal & Neonatal Hospital, Guangzhou Medical College, Guangzhou, Guangdong 510180, People’s Republic of China, e-mail dongshi3{at}yahoo.com.cn
To the Editor:
I read with interest the paper by Ho et al. (1), which described a rapid prenatal diagnostic test for simultaneous detection of Hb Barts hydrops fetalis and exclusion of maternal contamination. The main background to their study is that PCR-based techniques are highly sensitive and are also prone to false-positive results in prenatal diagnosis due to amplification of contaminating maternal DNA that may be present in the fetal samples. Current established PCR-based diagnostic tests require a separate test to exclude maternal contamination. Hence, the authors developed a novel quantitative fluorescent PCR (QF-PCR) assay that allowed diagnosis and exclusion of maternal contamination in one step. Their approach seemed excellent, with a sensitivity of 100% and specificity of 100%. However, I believe that the presented data did not justify use of the strategy in routine clinical practice.
First, the authors might add details about the incidence of misdiagnosis due to maternal contamination in fetal sampling. They cited a misdiagnosis rate of 3.8% attributable to maternal DNA contamination (2). Actually, this is a high rate of misdiagnosis, unacceptable for an experienced center. We acknowledge that maternal contamination is unavoidable in prenatal sampling, but measures can be taken to make contamination less likely. This problem is usually due to the inexperience of the operator at the time of sampling or of the laboratory technologist engaged in analyzing and separating the fetal material obtained. In our experience, the risk of maternal contamination in chorionic villous samples is remote with careful microscopic dissection to remove contaminating maternal decidua. For amniocentesis, samples contaminated heavily by blood can be cultured for 10–14 days before analysis. Culture of the cells reduces risk of maternal contamination. Although availability of a technique for differentiating tests is important, a low incidence of maternal contamination is vital. A QF-PCR test can easily detect the contamination, but it is no help to diagnosis. When maternal contamination is confirmed, a repeat sampling is usually required, which would add to the risk of contamination (i.e., 3.8%). In our experience in fetal sampling, the misdiagnosis rate due to maternal contamination in all fetal samples is 
1%.
Second, the QF-PCR approach might not decrease the cost for diagnosis. This technique usually requires both special materials, which increase adds to the cost of regular PCR, and instruments that are not available at most centers. In fact, clinical decision-making for pregnancies at risk for Hb Barts hydrops fetalis has been changing in regions with a high prevalence of 
-thalassemia. Ultrasonography now plays a major role in early detection of Hb Barts hydrops fetalis as early as 12–13 weeks, and can effectively differentiate normal pregnancies from those requiring an invasive evaluation (3)(4)(5), thus limiting invasive procedures to the few pregnancies identified to be at high risk by ultrasonography. This means that in 3 of 4 at-risk pregnancies, invasive procedures, which carry a 1% chance of miscarriage, are avoided. Because DNA study is relatively expensive, the medical saving might be noticeable. For the few centers with established QF-PCR services for aneuploidy testing, adding this multiplex approach to –SEA diagnosis would be simple and likely to be cost-effective.
Finally, not all prenatal testing requires a test for exclusion of maternal contamination suggested by the authors. For example, we use a regular multiplex Gap-PCR test to detect –SEA mutation of the -globin gene in fetal samples. If the genotype of the fetus is revealed to be – SEA /– SEA or /, there is no need to do a differentiating test. If the fetus is revealed to have the same genotype as the mother (–SEA /), maternal contamination should be considered. However, due to the high sensitivity and specificity of ultrasonography in detection of Hb Barts hydrops fetalis, few cases require a repeated sampling.
Acknowledgments
Grant/funding support: None declared.
Financial disclosures: None declared.
References
0-thalassemia. Ultrasound Obstet Gynecol 2006;28:173-177.[CrossRef][Web of Science][Medline]
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