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

Britta Runkel,Wiebke Sieben,Gregor Bein,Stephanie Polus,Dorothea Sow,Daniel Fleer

doi:10.1186/s12884-020-2742-4

Abstract

BackgroundAll 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.MethodsWe 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.ResultsNeither 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%]).ConclusionsNIPT for fetal RhD status is equivalent to conventional serologic testing using the newborn’s blood. Studies investigating patient-relevant outcomes are still lacking.

Highlights

All non-sensitized Rhesus D (RhD)-negative pregnant women in Germany receive antenatal Anti-D immunoglobulin (anti-D) prophylaxis without knowledge of fetal RhD status
During pregnancy, a Rhesus D (RhD)-negative woman may develop antibodies if her fetus is RhD-positive. These maternal allo-antibodies directed against fetal red cell surface antigens that the mother herself lacks can lead to hemolytic disease of the fetus and newborn (HDFN) [1]
Anti-D immunoglobulin administration was introduced in the early 1970s to reduce the incidence of alloimmunization of pregnant women to the D antigen and subsequently the incidence of HDFN, which has since decreased dramatically [2]

Summary

Introduction

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. We systematically reviewed the evidence on the benefit of NIPT for fetal RhD status in RhD-negative pregnant women. A Rhesus D (RhD)-negative woman may develop antibodies if her fetus is RhD-positive. These maternal allo-antibodies directed against fetal red cell surface antigens that the mother herself lacks can lead to hemolytic disease of the fetus and newborn (HDFN) [1]. The current policy is to administer anti-D to non-sensitized RhD-negative pregnant women in the 28th week of gestation [3]. The cord blood is phenotyped and postnatal anti-D prophylaxis is offered only if the newborn is RhD-positive.

Objectives

Methods

Results

Discussion

Conclusion