Targeted antenatal anti-D prophylaxis for RhD-negative pregnant women: a systematic review

Abstract

Background: All non-sensitized Rhesus D (RhD)-negative pregnant women in Germany receive antenatal anti-D prophylaxis without knowledge of fetal RhD status. Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma could avoid unnecessary anti-D administration. In this paper, we systematically reviewed the evidence on the benefit of NIPT for fetal RhD status in RhD-negative pregnant women. Methods: We systematically searched several bibliographic databases, trial registries, and other sources (up to October 2019) for controlled intervention studies investigating NIPT for fetal RhD versus conventional anti-D prophylaxis. The focus was on the impact on fetal and maternal morbidity. We primarily considered direct evidence (from randomized controlled trials) or if unavailable, linked evidence (from diagnostic accuracy studies and from controlled intervention studies investigating the administration or withholding of anti-D prophylaxis). The results of diagnostic accuracy studies were pooled in bivariate meta-analyses. Results: Neither direct evidence nor sufficient data for linked evidence were identified. Meta-analysis of data from about 60,000 participants showed high sensitivity (99.9%; 95% CI [99.5%; 100%] and specificity (99.2%; 95% CI [98.5%; 99.5%]). Conclusions: NIPT for fetal RhD status is equivalent to conventional serologic testing using the newborn's blood. Studies investigating patient-relevant outcomes are still lacking.

Diagnostic performance of the noninvasive prenatal FetoGnost RhD assay for the prediction of the fetal RhD blood group status

“…Recently, data from about 60.000 study participants were pooled in a large meta-analysis for the purpose to determine the diagnostic accuracy of NIPT RhD [20]. However, in this systematic review, only studies were included, which evaluated lab developed (in-house) tests.…”

“…Since the feasibility of targeted antenatal RAADP based on the result from a NIPT for the prediction of the fetal RhD status has been proposed by Dennis Lo's group and a Dutch group in 1998 it took about 12 years until the first nationwide program for targeted RAADP was implemented in Denmark [11][12][13]. Until today many validation studies have been published and extensively reviewed which revealed an excellent diagnostic accuracy of NIPT for RhD [14][15][16][17][18][19][20][21]. It has to be stressed in the given context that only false-negative NIPT RhD results may have relevant consequences (i.e., increased risk for anti-D alloimmunisation).…”

FIGO/ICM guidelines for preventing Rhesus disease: A call to action

“…Such a policy has recently been introduced into clinical practice in countries such as Denmark, the Netherlands, and the United Kingdom. A recent meta‐analysis of 60 000 participants showed that it has a very high sensitivity (99.9%; 95% CI, 99.5%–100%) and specificity (99.2%; 95% CI, 89.5%–99.5%) as compared with testing newborn's blood 21 . First‐trimester non‐invasive Rh(D) typing may therefore be used to prevent unnecessary administration of anti‐Rh(D) immunoglobulin in the course of pregnancy (routinely or following amniocentesis, etc.).…”

Laboratory Monitoring of Mother, Fetus, and Newborn in Hemolytic Disease of Fetus and Newborn

“…Presence of the fetal RHD gene indicates that the fetus is RhD positive. Since the first reports of cell-free fetal RHD in maternal plasma [16,17], noninvasive fetal RHD genotyping has become highly integrated into clinical medicine, and its accurate performance has been covered comprehensively in the literature [12,13,[18][19][20][21][22][23][24].…”