The role of non-invasive prenatal testing (NIPT) for fetal blood group typing in Australia.

Maternal alloimmunisation against red blood cell antigens can cause haemolytic disease of the fetus and newborn (HDFN). Although most frequently caused by anti-D, since the implementation of rhesus D (RhD) immunoglobulin prophylaxis, other alloantibodies have become more prevalent in HDFN. Recent advances in non-invasive prenatal testing (NIPT) have allowed early prediction of HDFN risk in alloimmunised pregnancies and allow clinicians to focus health resources on those pregnancies that require intervention. This article aims to provide updates on the current status of NIPT in Australia as both a diagnostic and screening tool in pregnancy.

Potential of Next-Generation Sequencing in Noninvasive Fetal Molecular Blood Group Genotyping.

Hemolytic disease of the fetus and newborn and fetal and neonatal alloimmune thrombocytopenia are caused by maternal antibodies against fetal alloantigens on red blood cells or platelets that are inherited from the father. After transplacental transport to the fetal circulation, antibodies of the IgG class may cause severe fetal anemia or bleeding complications. The indication for noninvasive fetal blood group genotyping is given if a clinically relevant antibody is detected in a pregnant woman and if the father is heterozygous (or unknown) for the implicated blood group allele. This mini-review will focus on the advantages and current limitations of next-generation sequencing (NGS) for noninvasive diagnosis of fetal blood groups which is, in contrast to fetal aneuploidy screening, proposed only by some research groups. Targeted massively parallel sequencing of short DNA fragments from maternal cell-free plasma samples enables counting of fetal alleles for many single nucleotide polymorphisms in parallel. This information can be utilized for estimation of the fetal fraction of cell-free DNA (cfDNA) as well as detection of the paternal blood group allele in question. Adherence to a cut-off of ≥4% fetal fraction for reporting conclusive results is recommended to avoid false-negative results due to low fetal fraction. For screening purposes of fetal RHD in RhD-negative pregnant women, real-time PCR methods are very well established. However, for diagnostic purposes, the targeted amplicon-based NGS approach has the inherent capability to estimate the fetal fraction of cfDNA. In the future, improving the accuracy of NGS by consensus sequencing of single cfDNA molecules may enable reliable fetal blood group genotyping already in the first trimester of pregnancy.

A study on the noninvasive prenatal diagnosis of fetal blood type by maternal blood / 预防医学

Objective ToexplorethevalueofprenataldiagnosisoffetalABObloodgroupsinthepreventionofABO-HDN,andtoprovideevidenceforpreventionofABO-HDN.Methods Atotalof3777sampleswerecollectedfromthe pregnant women whose ABO blood group is O,and we detected the ABO blood group by serological method to detect the titerofIgGanti-Aandanti-Binthematernalblood.Results Amongthe3777samplescollectedfromthepregnant women whose ABO blood group is O ,the titer of IgG anti-A to anti-B was 1 to1 024 in 27 samples(0.7%),1∶51 2 in 97 samples(2.6%),1∶256 in 1 63 samples(4.3%),1∶1 28 in 285 samples(7.5%)and 1:64 in 603 samples(1 6%). We followed the pregnancy and newborn outcome of 769 case whose antibody titer of 1∶64 or more ,and compared the fetal ABO blood group with results of the titer of IgG anti -A and/or anti -B.A total of 641 patients (83.3%) was corresponding resistance against A or B,and 1 28 patients (1 6.6%)was not corresponding resistance against A or B.The higher the antibody titer,the higher incidence of neonatal ABO hemolytic disease occurred.We extracted the fetal free DNA of peripheral blood plasma in 30 pregnant women, and the genotypes of fetal ABO blood group were detected by the polymerase chain reaction-sequence specific primer (PCR-SSP),and all the experiment presented success.Conclusion ThetiterofIgGanti-Atoanti-Bcouldbeusedtopreventtheoccurrenceofhemolyticdiseaseofnewborn. Considering the interference factors,the fetal free DNA in the maternal circulation could be used to prenatally detect fetal ABO blood groups.