Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis: prospective cohort study of a nationwide programme in the Netherlands.
OBJECTIVE
To determine the accuracy of non-invasive fetal testing for the RHD gene in week 27 of pregnancy as part of an antenatal screening programme to restrict anti-D immunoglobulin use to women carrying a child positive for RHD DESIGN:  Prospectively monitoring of fetal RHD testing accuracy compared with serological cord blood typing on introduction of the test. Fetal RHD testing was performed with a duplex real time quantitative polymerase chain reaction, with cell-free fetal DNA isolated from 1 mL of maternal plasma The study period was between 4 July 2011 and 7 October 2012. The proportion of women participating in screening was determined.


METHODS
Nationwide screening programme, the Netherlands. Tests are performed in a centralised setting.


METHODS
25 789 RhD negative pregnant women.


METHODS
Sensitivity, specificity, false negative rate, and false positive rate of fetal RHD testing compared with serological cord blood typing; proportion of technical failures; and compliance to the screening programme.


RESULTS
A fetal RHD test result and serological cord blood result were available for 25 789 pregnancies. Sensitivity for detection of fetal RHD was 99.94% (95% confidence interval 99.89% to 99.97%) and specificity was 97.74% (97.43% to 98.02%). Nine false negative results for fetal RHD testing were registered (0.03%, 95% confidence interval 0.01% to 0.06%). In two cases these were due to technical failures. False positive fetal RHD testing results were registered for 225 samples (0.87%, 0.76% to 0.99%). Weak RhD expression was shown in 22 of these cases, justifying anti-D immunoglobulin use. The negative and positive predictive values were 99.91% (95% confidence interval 99.82% to 99.95%) and 98.60% (98.40% to 98.77%), respectively. More than 98% of the women participated in the screening programme.


CONCLUSIONS
Fetal RHD testing in week 27 of pregnancy as part of a national antenatal screening programme is highly reliable and can be used to target both antenatal and postnatal anti-D immunoglobulin use.
Department of Experimental Immunohematology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.|Center for Clinical Transfusion Research, Sanquin Research and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden.|Department of Immunohematology Diagnostic Services, Sanquin Research, Amsterdam, Netherlands.
Masja
M
de Haas
Department of Experimental Immunohematology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.|University Medical Center Utrecht, Division Woman and Baby, Department of Obstetrics, Utrecht, Netherlands.
Florentine F
FF
Thurik
Netherlands Organization for Applied Scientific Research, Department of Child Health, Leiden, Netherlands.
Catharina P B
CP
van der Ploeg
Department of Experimental Immunohematology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.|Department of Immunohematology Diagnostic Services, Sanquin Research, Amsterdam, Netherlands.
Barbera
B
Veldhuisen
National Institute for Public Health and the Environment, Service for vaccine provision and prevention programs, Bilthoven, Netherlands.
Hoang
H
Hirschberg
Department of Experimental Immunohematology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
Aicha Ait
AA
Soussan
Department of Immunohematology Diagnostic Services, Sanquin Research, Amsterdam, Netherlands.
Heleen
H
Woortmeijer
National Institute for Public Health and the Environment, Center for population screening, Bilthoven, Netherlands.
Frithjofna
F
Abbink
University Medical Center Utrecht, Division Woman and Baby, Department of Obstetrics, Utrecht, Netherlands.
Godelieve C M L
GC
Page-Christiaens
University Medical Center Utrecht, Division Woman and Baby, Department of Obstetrics, Utrecht, Netherlands.
Peter G
PG
Scheffer
Department of Experimental Immunohematology, Sanquin Research, Amsterdam and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
C
C
Ellen van der Schoot
D004247:DNA / Q000302:isolation & purification; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D009426:Netherlands; D011237:Predictive Value of Tests; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012203:Rh Isoimmunization / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D012204:Rh-Hr Blood-Group System / Q000235:genetics*; D018029:Rho(D) Immune Globulin / Q000008:administration & dosage / Q000235:genetics; D012680:Sensitivity and Specificity
D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; D004247:DNA