Researchers in the UK have taken the next step towards the introduction of a test which could help identify the rhesus negative pregnant women who are carrying a rhesus negative baby. These women would then not even need to consider whether or not they wished to have antenatal Anti-D. The test is carried out on maternal blood and can be done at the same time as other blood tests in pregnancy.
In the UK, some 40,000 women a year are offered antenatal Anti-D despite the fact that they are carrying a rhesus negative baby. But if a woman is pregnant with a rhesus negative baby, she is not at risk of isoimmunisation. My previous post on this topic discusses the wider situation and some of the research background to this area, including a Spanish study showing that determining the blood status of the baby from blood taken from its mother in early pregnancy was both feasible and accurate.
A larger study
Now a team has carried out research on the same topic. This is an even larger study which not only included more women, but which analysed blood samples taken at multiple points in pregnancy.
Women from seven UK hospital Trusts were asked to donate an extra 4ml of blood at their booking visit and every time they had a routine blood test. These samples were analysed for fetal Rh status. The researchers were able to gather 4913 samples from 2288 women. They then checked the results of the tests carried out on these samples against the baby’s blood type at birth. The results confirmed that, from 11 completed weeks of pregnancy, the test is highly sensitive. Before 11 weeks, the incidence of false RhD negative test results was 16/865, or 1.86%.
The authors’ conclusion?
That “Mass throughput fetal RHD genotyping is sufficiently accurate to be used from 11 weeks’ gestation. To maximise reduction in administration of anti-RhD immunoglobulin and to minimise costs to both women and health services, testing should be performed as soon as possible from 11 weeks’ gestation to coincide with routine antenatal visits.” (Chitty et al 2014)
The “allowed” problem
One thing bothers me about the wording of this. The researchers comment that, “When third trimester testing confirmed that the fetus was RHD negative, women were allowed to opt out of receiving anti-RhD immunoglobulin if they requested to do so as the reliability of testing at this gestation is proved.” (Chitty et al 2014).
Women do not need to be *allowed* to opt opt of receiving anti-RhD immunoglobulin.
Women do not need to be ALLOWED to opt out of anything.
It is always their decision whether or not to have this pooled human plasma product, and regardless of whether or not the reliability of any test is proven or otherwise. This unfortunate turn of phrase, however, is the only problematic element in a study which will hopefully be another step on the important path towards reducing the number of women who are given anti-D that their future children cannot possibly benefit from.
Objectives To assess the accuracy of fetal RHD genotyping using cell-free fetal DNA in maternal plasma at different gestational ages.
Design A prospective multicentre cohort study.
Setting Seven maternity units in England.
Participants RhD negative pregnant women who booked for antenatal care before 24 weeks’ gestation.
Interventions Women who gave consent for fetal RHD genotyping had blood taken at the time of booking for antenatal care and, when possible, at other routine visits such as for Down’s syndrome screening between 11 and 21 weeks’ gestation, at the anomaly scan at 18-21 weeks, and in the third trimester when blood was taken for the routine antibody check. The results of cord blood analysis, done routinely in RhD negative pregnancies, were also obtained to confirm the fetal RHD genotyping.
Main outcome measures The accuracy of fetal RHD genotyping compared with RhD status predicted by cord blood serology.
Results Up to four analyses per woman were performed in 2288 women, generating 4913 assessable fetal results. Sensitivity for detection of fetal RHD positivity was 96.85% (94.95% to 98.05%), 99.83% (99.06% to 99.97%), 99.67% (98.17% to 99.94%), 99.82% (98.96% to 99.97%), and 100% (99.59% to 100%) at <11, 11-13, 14-17, 18-23, and >23 completed weeks’ gestation, respectively. Before 11 weeks’ gestation 16/865 (1.85%) babies tested were falsely predicted as RHD negative.
Conclusions Mass throughput fetal RHD genotyping is sufficiently accurate for the prediction of RhD type if it is performed from 11 weeks’ gestation. Testing before this time could result in a small but significant number of babies being incorrectly classified as RHD negative. These mothers would not receive anti-RhD immunoglobulin, and there would be a risk of haemolytic disease of the newborn in subsequent pregnancies.