Recombinant anti-D for prevention of maternal-foetal Rh(D) alloimmunization: a randomized multi-centre clinical trial

Abstract

Objective To compare the efficacy and safety of recombinant anti-D (R-anti-D) with conventional polyclonal anti-D (Poly anti-D) in preventing maternal-fetal rhesus D (RhD) alloimmunization and to investigate the immunogenicity of R-anti-D. Methods This was a randomized, open-label, multi-center clinical trial conducted in RhD-negative pregnant women who did not receive antenatal anti-D who delivered RhD-positive babies and showed negative indirect Coombs tests (ICTs) at baseline. The women were randomized in a 2:1 ratio to R-anti-D or Poly anti-D groups and were administered 300 mcg (IM) of the corresponding drug within 72 hours of delivery. ICT was performed 72 hours, 90 days, and 180 days after anti-D injection. Serum samples were collected to check for the development of antibodies against R-anti-D at days 90 and 180, using bridging enzyme-linked immunosorbent assay. The proportion of subjects who had positive ICT results at days 90 and 180 were compared between the groups using Fisher's exact test. Results A total of 144 women were randomized to the R-anti-D group and 71 to the Poly anti-D group. Three women in the R-anti-D and none in the Poly anti-D group had a positive ICT result at day 90. No woman in either group had positive ICT result at day 180. Both drugs were well tolerated with only 4 reports of adverse events in each group-all were mild, non-serious, and resolved without sequelae. No subject developed antibodies against R-anti-D. Conclusion The studied R-anti-D is comparable in efficacy to conventional Poly anti-D and is safe and non-immunogenic.

Rho(D) Immune Globulin (anti-D) Concentration-Time Curve After Antenatal Immunoprophylaxis in RhD-Negative Pregnant Women

“…Replace anti-D supply expenses in pregnant women with RhD-negative fetuses by noninvasive prenatal testing, although might not reduce costs, brings signi cant bene ts for perinatal care (Clausen and Hellberg 2020;Darlington et al 2018;Ryczek et al 2020;Schmidt et al 2014). Another measure is recombinant anti-D (Mayekar et al 2020) as a substitute for anti-D currently produced from human plasma, which, despite all widely proven safety, does not extinguish minimum risks inherent of a blood product. However, until these techniques can be universally offered, HDFN prophylaxis by administering anti-D immunoglobulin to all RhD-negative pregnant women with positive or unknown RhD partner remains the gold standard for this issue.…”

CNest: A Novel Copy Number Association Discovery Method Uncovers 862 New Associations from 200,629 Whole Exome Sequence Datasets in the UK Biobank

“…It is still unclear what potential benefit the RHD gene deletion may have that merits its relatively high frequency in the human population (136). Blood tests are normally carried out in D-negative expectant mothers to determine the Rh factor status of the child and direct treatment if using anti-D injection is required (137). However variation in the less well understood Rh C and E alleles of RHCE is clinically relevant, influences the risk of HDN (138) and this association discovered in this study merits further investigation for this well understood risk factor for pregnancy.…”

Curva da concentração de imunoglobulina anti-RhD após imunoprofilaxia pré-natal em gestantes RhD negativo

“…In these cases, anti-D administration was not necessary, as there will be no possibility of maternal sensitization by fetal RhD antigen, subjecting pregnant woman to a blood product and its tiny risks in an unnecessary way, in addition to the expendable cost of anti-D. [2] Replace anti-D supply expenses in pregnant women with RhD-negative fetuses by noninvasive prenatal testing, although might not reduce costs, brings significant benefits for perinatal care. [9,[22][23][24] Another measure is recombinant anti-D [25] as a substitute for anti-D currently produced from human plasma, which, despite all widely proven safety, does not extinguish minimum risks inherent of a blood product. However, until these techniques can be universally offered, HDFN prophylaxis by administering anti-D immunoglobulin to all RhD-negative pregnant women with positive or unknown RhD partner remains the gold standard for this issue.…”

“…23 A IgM, devido ao seu alto peso molecular, é incapaz de cruzar a placenta, 24 tornando muito rara a possibilidade de hemólise das hemácias fetais na primeira gravidez de feto RhD positivo, exceto nos casos de gestantes já imunizadas previamente. 25 Na exposição subsequente inicia-se a imunização secundária, caracterizada pela intensa e rápida produção (em poucos dias) de imunoglobulina G (IgG), a principal classe de imunoglobulina (Ig) e a única capaz de ultrapassar a barreira placentária. 26,27 Ao atingir a corrente sanguínea fetal, a IgG reconhece e se liga aos antígenos RhD da superfície dos eritrócitos fetais, promovendo a opsonização e estimulando a destruição desses eritrócitos por hemólise, causando a doença hemolítica do feto e do recém-nascido.…”

“…No entanto, em casos mais severos podem ocorrer complicações com potencial de causar óbito fetal ou neonatal. 25,31 Para o diagnóstico da aloimunização materna e consequente manejo de possível doença hemolítica do feto e do recém-nascido utiliza-se a pesquisa de anticorpos irregulares (PAI), a qual fundamenta-se no teste indireto de antiglobulina humana, denominação atualmente utilizada em substituição ao teste de Coombs indireto, termo que ainda permanece entre os descritores em saúde. O teste detecta in vitro a presença de anticorpos irregulares no soro materno, e possibilita a determinação da titulação quando o anticorpo está presente.…”