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Detection of fetal Rhesus D gene in whole blood of women booking for routine antenatal care [Eur J Obstet Gynecol Reprod Biol 2003;108:29–32]
European Journal of Obstetrics & Gynecology and Reproductive Biology 110 (2003) 117
Letter to the Editor Detection of fetal Rhesus D gene in whole blood of women booking for routine antenatal care [Eur J Obstet Gynecol Reprod Biol 2003;108:29–32] Turner et al. [1] recently reported 82% accuracy in prediction of fetal RhD status from maternal whole blood before 20 weeks gestation. False negative results led the authors to conclude that further research must be performed before RhD typing from maternal blood can be introduced into clinical practice. We have recently published a study [2] describing fetal RhD typing from maternal blood with 100% accuracy in 137 pregnancies (mostly second trimester) using similar methods. We used plasma, as it contains a higher proportion of fetal DNA than the cellular fraction of maternal blood. In our study, the quantity of total DNA was lower (range 0.5–4.5 mg/ml plasma) than that reported by Turner et al. (>100 mg/ml blood) whereas the maximum number of copies of fetal DNA detected were more similar. We suggest that the increased background of maternal DNA may have reduced the sensitivity of fetal DNA detection. Furthermore, Turner et al. used a very small fraction of the extracted DNA (equivalent of 10–30 ml blood) compared to our study (equivalent of 80 ml plasma) and performed less replicates. Turner et al. point out that previous studies have involved potentially complicated pregnancies in which levels of fetal DNA may be elevated. In our study, 30 samples were from women undergoing an invasive procedure for karyotyping but the remaining 107 were from ongoing pregnancies of women with anti-D. The high accuracy in fetal RhD typing from maternal plasma in our study led to the introduction of this test in May 2001 into clinical practice at the International Blood Group Reference Laboratory (IBGRL) in Bristol, UK (part of the National Blood Service) (http://www.blood.co.uk/ibgrl). The test is currently being used to predict fetal RhD status in alloimmunised women referred via their fetal medicine centre from 16 weeks gestation.
We completely agree with Turner et al. that further larger scale studies need to be performed for non-immunised Dnegative women with normal pregnancies. This is especially important since the National Institute for Clinical Excellence (NICE) recommended in May 2002, that all nonimmunised D-negative pregnant women should receive routine antenatal anti-D prophylaxis at 28 and 34 weeks in UK and Wales [3]. NICE have fully endorsed research into methods of mass-testing plasma from all D-negative pregnant women, so that anti-D is administered only where it is needed and IBGRL and other groups are pursuing research in this area.
References [1] Turner MJ, Martin CM, O’Leary JJ. Detection of fetal Rhesus D gene in whole blood of women booking for routine antenatal care. Eur J Obstet Gynecol Reprod Biol 2003;108:29–32. [2] Finning KM, Martin PG, Soothill PW, Avent ND. Prediction of fetal D status from maternal plasma: introduction of a new noninvasive fetal RHD genotyping service. Transfusion 2002;42:1079–85. [3] Guidance on the use of routine antenatal anti-D prophylaxis for RhDnegative women, National Health Service, National Institute for Clinical Excellence, Technology Appraisal Guidance No. 41, May 2002.
0301-2115/$ – see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0301-2115(03)00285-9
Kirstin Finning* Geoff Daniels Peter Martin International Blood Group Reference Laboratory National Blood Service, Southmead Road Bristol BS10 5ND, UK * Corresponding author. Tel.: þ44-117-991-2126/2122 fax: þ44-117-959-1660 E-mail address: [email protected] (K. Finning) Peter Soothill Department of Obstetrics and Gynecology University of Bristol, Bristol, UK 18 May 2003
Letter to the Editor Detection of fetal Rhesus D gene in whole blood of women booking for routine antenatal care [Eur J Obstet Gynecol Reprod Biol 2003;108:29–32] Turner et al. [1] recently reported 82% accuracy in prediction of fetal RhD status from maternal whole blood before 20 weeks gestation. False negative results led the authors to conclude that further research must be performed before RhD typing from maternal blood can be introduced into clinical practice. We have recently published a study [2] describing fetal RhD typing from maternal blood with 100% accuracy in 137 pregnancies (mostly second trimester) using similar methods. We used plasma, as it contains a higher proportion of fetal DNA than the cellular fraction of maternal blood. In our study, the quantity of total DNA was lower (range 0.5–4.5 mg/ml plasma) than that reported by Turner et al. (>100 mg/ml blood) whereas the maximum number of copies of fetal DNA detected were more similar. We suggest that the increased background of maternal DNA may have reduced the sensitivity of fetal DNA detection. Furthermore, Turner et al. used a very small fraction of the extracted DNA (equivalent of 10–30 ml blood) compared to our study (equivalent of 80 ml plasma) and performed less replicates. Turner et al. point out that previous studies have involved potentially complicated pregnancies in which levels of fetal DNA may be elevated. In our study, 30 samples were from women undergoing an invasive procedure for karyotyping but the remaining 107 were from ongoing pregnancies of women with anti-D. The high accuracy in fetal RhD typing from maternal plasma in our study led to the introduction of this test in May 2001 into clinical practice at the International Blood Group Reference Laboratory (IBGRL) in Bristol, UK (part of the National Blood Service) (http://www.blood.co.uk/ibgrl). The test is currently being used to predict fetal RhD status in alloimmunised women referred via their fetal medicine centre from 16 weeks gestation.
We completely agree with Turner et al. that further larger scale studies need to be performed for non-immunised Dnegative women with normal pregnancies. This is especially important since the National Institute for Clinical Excellence (NICE) recommended in May 2002, that all nonimmunised D-negative pregnant women should receive routine antenatal anti-D prophylaxis at 28 and 34 weeks in UK and Wales [3]. NICE have fully endorsed research into methods of mass-testing plasma from all D-negative pregnant women, so that anti-D is administered only where it is needed and IBGRL and other groups are pursuing research in this area.
References [1] Turner MJ, Martin CM, O’Leary JJ. Detection of fetal Rhesus D gene in whole blood of women booking for routine antenatal care. Eur J Obstet Gynecol Reprod Biol 2003;108:29–32. [2] Finning KM, Martin PG, Soothill PW, Avent ND. Prediction of fetal D status from maternal plasma: introduction of a new noninvasive fetal RHD genotyping service. Transfusion 2002;42:1079–85. [3] Guidance on the use of routine antenatal anti-D prophylaxis for RhDnegative women, National Health Service, National Institute for Clinical Excellence, Technology Appraisal Guidance No. 41, May 2002.
0301-2115/$ – see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S0301-2115(03)00285-9
Kirstin Finning* Geoff Daniels Peter Martin International Blood Group Reference Laboratory National Blood Service, Southmead Road Bristol BS10 5ND, UK * Corresponding author. Tel.: þ44-117-991-2126/2122 fax: þ44-117-959-1660 E-mail address: [email protected] (K. Finning) Peter Soothill Department of Obstetrics and Gynecology University of Bristol, Bristol, UK 18 May 2003