Noninvasive prenatal screening for RHD: the 1st national antenatal directed anti-D prophylaxis program – the Danish model or a guide to robust prediction of need of anti-D

Background As of January 1, 2010, Denmark implemented a national antenatal directed anti-D prophylaxis program. Prior to this, only postnatal prophylaxis directed by serology of cord blood was practiced. A preparatory work for modernization and optimization of fetal care was carried out by the National Board of Health with participation of leading obstetricians, specialists in fetal medicine, general practitioners, midwives, clinical immunologists and administrators. The promising results of non-invasive prenatal diagnosis based on cell free fetal DNA enabled an antenatal directed use of anti-D to those with a D positive fetus, thus eliminating approximately 40% of the antenatal use of anti-D. The complete program now includes an antenatal RHD screening in gestational week 25, and a postnatal serological RhD typing of cord blood, in both instances followed by administration of anti-D to those found positive. Aim The explicit aim of the RHD screening was to obtain the highest possible sensitivity to recommend anti-D in all cases where it might be indicated whereas specificity was of secondary priority. Methods Health services in Denmark are organized in five regions; accordingly screening has been implemented in every region, each using its own in-house screening methodology. However, all regions have implemented automated DNA purification and the assays are variations over a theme of multiple PCRs covering several exons. A control reaction for DNA purification is obligatory. However, a control for fetal DNA is not included. A working group with members from all regions has implemented a national scheme for quality control. Digital on-line delivery of results to general practitioners, midwives and obstetricians is implemented in most regions thus cutting down on cost and time. Results The continuation of postnatal serology has allowed a quality control of RHD screening. During the first six months of screening only two false negative results occurred out of 2312 tested (0·087%) suggesting a sensitivity of 99·9%. Due to the sacrifice of specificity some unnecessary use of anti-D occurred, 39 cases or 1·7%. Discussion The elimination of 38·3% of the use of anti-D, that is unnecessary and the related clinical contacts balances the expenses for the screening. An unforeseen benefit of the screening has emerged. The availability of the antenatal RHD results at the time of delivery has simplified logistics and preliminary clinical action is taken based on the antenatal result. Only in the very rare occasions of a (false negative) discrepancy between antenatal and postnatal results is communication needed between laboratory, clinician, and patient. The challenge will be to maintain the high standards in a possible future setting without serology serving as a benchmark for quality control.