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PubMedDate not supplied

Management of anti-Rhesus-D antibodies in pregnancy: a review from 1994 to 1998.

OBJECTIVE: To review our management of anti-Rhesus-D antibodies in pregnancy over a 5-year period in order to assess possible changes in the management or prognosis which may have developed with time. METHOD: Retrospective analysis of prospectively collected data from 31 pregnancies with maternal anti-D levels >4 IU/ml and in which the fetus was Rhesus positive. RESULTS: There were a total of 30 amniocenteses, 8 cordocenteses, and 54 fetal blood transfusions performed. When undertaken as the first procedure, the mean gestational age at amniocentesis was 30 weeks as compared with 25 weeks for fetal blood sampling/transfusion (p < 0.05). The median anti-D level at the first procedure was 24 IU/ml for amniocentesis and 64 IU/ml for fetal blood sampling. Of the 54 blood transfusions, 43 were intravascular, 4 were intraperitoneal, and 7 transfusions were both intravascular and intraperitoneal. CONCLUSIONS: Intravascular as opposed to intraperitoneal transfusions were found to be the main method of transfusion in the later years in this study, a finding which was expected with improved sonographic equipment. Apart from this, management and prognosis of anti-D red cell isoimmunisation in pregnancy have remained relatively stable since the 1980s. Amniocentesis was useful in the management of such pregnancies, especially as an initial procedure in the cases with a lower initial anti-D level. In this series 90% of the fetuses requiring blood transfusion, but were without hydrops, survived, whereas this was about 70%, if they had become hydropic (this latter figure was reduced by 2 hydropic deaths before 20 weeks' gestation in the same very severely affected woman).

Amniocentesis↗
PubMedDate not supplied

Fetal hemolytic disease due to anti-Rh17 alloimmunization.

OBJECTIVE: To delineate clinical features of a case of fetal hemolytic disease due to anti-Rh17, along with a review of relevant studies published in English and Japanese. METHODS: We present clinical features of a -D-/-D- phenotype woman with anti-Rh17 alloimmunization during pregnancy. Relevant English literature in the MEDLINE database was reviewed, while Japanese studies were searched in the Japana Centra Revuo Medicina database. RESULTS: A Japanese -D-/-D- woman with anti-Rh17 (Hro) was treated during pregnancy. Serial ultrasonography, antibody titers, amniocenteses, and cordocenteses were conducted for perinatal management. Amniocentesis results demonstrated a high delta optical density level of 450 in the amniotic fluid, while cordocentesis revealed alloimmunization between the mother and the fetus as well as fetal hemolytic anemia. Blood flow velocity in the middle cerebral artery indicated a rapid development of fetal anemia. The newborn demonstrated severe anemia and hyperbilirubinemia, which were successfully treated with exchange transfusions. Two cases of prenatally diagnosed fetal hemolytic disease due to anti-Rh17 were found published in English and 5 in Japanese. CONCLUSION: A -D-/-D- phenotype patient with anti-Rh17 was successfully managed during pregnancy and a good outcome for the neonate was achieved. Our results and a review of related literature led to the following suggestions. The first pregnancy in a -D-/-D- woman may be affected, an anamnestic immune response can easily occur during pregnancy, the level of anti-Rh17 titer is indicative of the degree of fetal hemolysis, and appropriate intrauterine intervention is warranted for achievement of a good outcome.

Adult↗
PubMed1990

Important variations of maternal anti-Rhesus (D) antibody level during two consecutive pregnancies without antigenic stimulus.

In many cases, during pregnancies of anti-D alloimmunized women, without antigenic stimulus, the anti-D concentration remains stable. We report here a case of a woman anti-D and anti-C alloimmunized which has presented high variation of anti-D concentration in her serum during two successive pregnancies with a Rh-negative fetus. Thus, the Liley Index only has confirmed the absence of fetal damage.

Adult↗
PubMed1992

Parity-related prevalence of rhesus antigens among Mozambican parturients.

The potential risk of rhesus alloimmunization and the ensuing risk of fetal death with increasing parity were investigated in two groups of parturients; primiparous and grand multiparous (para > or = 5) women with liveborns. It was hypothesized that significantly fewer women of the latter than of the former group would be rhesus negative, since grand multiparity would be expected to be associated with an increased risk of late fetal death in rhesus-negative parturients. Primiparous (n = 390) and grand multiparous (n = 755) parturients with liveborns were studied in order to identify D- and Du-negative individuals. Sixteen out of 390 primiparas (4.10%) and 28/755 (3.71%) grand multiparas were D and Du negative. The difference did not reach statistical significance. It appears that being a D- and Du-negative grand multiparous parturient, in the absence of anti-D prophylaxis, is not a significant reproductive disadvantage to being primipara in terms of an increased risk of having stillborn babies.

ABO Blood-Group System↗
PubMed1992

Role of rhesus alloimmunization in the etiology of late fetal death in Maputo.

Grand multiparous parturients with unexplained late fetal death (n = 70) and with surviving newborns (n = 755) were analyzed and compared regarding blood group in general and presence of D and Du antigens in particular. In the stillbirth group, none of the parturients had any signs of disease (syphilis, preeclampsia, placental abruption, severe anemia or fever) that could be associated with the fetal death. It was found that none of the parturients with stillbirth were D- and Du-negative while 28/755 (3.71%) of parturients with liveborn babies were D- and Du-negative. It is concluded that, among grand multiparous parturients with otherwise unexplained late fetal death, the risk of having fetomaternal rhesus incompatibility as stillbirth etiology is insignificant. The advantage of introducing anti-D immunoglobulin for prophylaxis against rhesus alloimmunization would presumably be insignificant.

Developing Countries↗
PubMed2002

Rare RHCE phenotypes in black individuals of Afro-Caribbean origin: identification and transfusion safety.

The molecular backgrounds of variants encountered in Afro-Caribbean black individuals and associated with the production of clinically significant antibodies against high-incidence antigens (anti-RH18, anti-RH34) and against Rhe epitopes were determined. We showed that RH:-18 phenotypes are produced by 3 distinct RHCE alleles: ceEK carrying 48G>C (exon 1), 712A>G, 787A>G, 800T>A (exon 5); ceBI carrying 48G>C (exon 1), 712A>G (exon 5), 818C>T (exon 6), 1132C>G (exon 8); and the already known ceAR allele carrying 48G>C (exon 1), 712A>G, 733C>G, 787A>G, 800T>A (exon 5), and 916A>G (exon 6). The RH:-34 phenotype is produced by the (C)ce(s) haplotype described previously and composed of a hybrid D-CE(3-8)-D gene with 4 extra mutations next to a ce(s) allele (733C>G; exon 5) with an extra mutation in exon 7 (1006G>T). Partial Rhe with risk of immunization against lacking epitopes can be produced by the new ce(s) allele carrying an extra mutation in exon 3 (340C>T) and by the ceMO allele described previously. A population of sickle cell disease patients was screened to estimate the incidence of these rare alleles, with the conclusion that a procedure is required to detect the associated phenotypes in black donors to ensure transfusion safety for patients. We also described a new variant [ce(s)(748)] and variants carrying different altered alleles in nonimmunized patients and for whom the risk of immunization is discussed.

Alleles↗
PubMed2002

The DAU allele cluster of the RHD gene.

Variant D occurs frequently in Africans. However, considerably less RHD alleles have been described in this population compared with Europeans. We characterized 5 new RHD alleles, dubbed DAU-0 to DAU-4, that shared a T379M substitution and occurred in a cDe haplotype. DAU-1 to DAU-4 were detected in Africans with partial D phenotypes. They harbored one and 2 additional missense mutations, respectively, dispersed throughout the RhD protein. An anti-D immunization was found in DAU-3. DAU-0 carrying T379M only was detected by screening European blood donors and expressed a normal D phenotype. Within the phylogeny of the RHD alleles, DAU formed an independent allele cluster, separate from the DIVa, weak D type 4, and Eurasian D clusters. The characterization of the RH phylogeny provided a framework for future studies on RH alleles. The identification of the DAU alleles increased the number of known partial D alleles in Africans considerably. DAU alleles may be a major cause of antigen D variability and anti-D immunization in patients of African descent.

Africa↗
PubMed2002

DNB: a partial D with anti-D frequent in Central Europe.

To improve routine D typing and define transfusion strategy, it is important to establish the frequency of partial D alleles and their susceptibility to anti-D alloimmunization due to transfusion or pregnancy. We identified the partial D DNB that was caused by an RHD(G355S) allele associated with a CDe haplotype and whose phenotype presented a normal D in routine typing. The antigen density was about 6000 D antigens per red blood cell, and the Rhesus index was 0.02. Five anti-D immunization events with allo-anti-D titers up to 128 were observed. Twelve carriers of DNB were whites of Central Europe; the only Danish proband had Austrian ancestry. DNB was the most frequent partial D recognized so far in whites, occurring with frequencies of up to 1:292 in Switzerland. DNB was the underlying partial D phenotype in a relevant fraction of anti-D immunizations occurring in whites.

Alleles↗
PubMed2004

A clinical service in the UK to predict fetal Rh (Rhesus) D blood group using free fetal DNA in maternal plasma.

Antenatal determination of fetal blood group is important in pregnancies with a significant risk of hemolytic anemia due to maternal alloimmunization. The International Blood Group Reference Laboratory (part of the National Blood Service) in Bristol, UK, provides a fetal blood group genotyping service to obstetricians caring for immunized pregnant women with heterozygous partners. Since 2001, fetal D typing has been offered using free fetal DNA in maternal plasma. Real-time polymerase chain reaction (PCR) assays are performed to detect the RHD gene. To confirm the presence of fetal DNA when RHD is not detected, Y-chromosome sequences are targeted. When a D-negative female fetus is predicted, maternal buffy coat DNA is tested for eight insertion/deletion polymorphisms. Sequences that are absent from the maternal genome are then targeted in maternal plasma and are used to confirm the presence of free fetal DNA in the blood sample. Currently, 283 pregnancies have been tested, of which 50 are awaiting confirmatory results. Fetal D status was correctly predicted in 223 cases, and no result was obtainable in 7 cases. In three cases, serology on cord blood was discrepant with reported results, but all fetuses had received multiple intrauterine transfusions. The new test has significantly reduced the number of invasive procedures carried out in the UK for fetal D grouping. Antenatal anti-D prophylaxis is currently being introduced in the UK to all D-negative women; in the future, detection of fetal RHD sequences in maternal plasma may allow anti-D to be restricted to pregnancies involving a D-positive fetus.

Antigens, Human Platelet↗
PubMed2003

Factors associated with vertical HIV transmission during two different time periods: the impact of zidovudine use on clinical practice at a Brazilian reference centre.

Vertical HIV transmission rates and associated factors among mother-infant pairs cared for at a Brazilian reference centre from 1988 to 1993 (period 1), and from 1996 to 1999 (period 2) were evaluated. A total of 150 and 239 infants born to HIV+ mothers were enrolled at birth during these periods. No zidovudine prophylaxis was available in period 1. In period 2, 92.4% of the infants were exposed to zidovudine (54% started at delivery or in the post-natal period). During period 1, 25 of 129 infants were found to be infected (19.4%; 95% confidence interval [CI]=13-27) vs 20 of 232 (8.6%; 95% CI=5-13) during period 2 (P <0.01). After controlling for co-variables, this decline was due to zidovudine prophylaxis, either with complete (odds ratio [OR]=0.24; 95% CI=0.08-0.70) or incomplete (OR=0.37; 95% CI=0.17-0.81) regimens. Premature rupture of membranes (OR =3.2) and rhesus-negative blood type of the infant (OR=2.6) facilitated transmission. Although confirming the protective effect of zidovudine prophylaxis, alternative approaches aimed at pregnant women identified late are needed for this population.

Adolescent↗
PubMed1998

The decline in Rh hemolytic disease: should Rh prophylaxis get all the credit?

OBJECTIVES: This study sought to quantify the magnitude of Rh disease reduction occurring secondary to Rh prophylaxis and other determinants. METHODS: Outcomes considered included maternal Rh sensitization, neonatal Rh disease, and perinatal deaths from Rh disease. Analysis was based on Poisson regression modeling of ecological data from Manitoba, Canada, and conditional probability modeling. RESULTS: The ecological analysis showed that changes in birth order and Rh prophylaxis resulted in 24% (95% confidence interval [CI] = 1% 42%) and 69% (95% CI = 61%, 76%) decreases, respectively, in Rh sensitizations (D and non-D) in Manitoba between 1963 and 1988. Rh prophylaxis and nonprogram factors were responsible for 83% (95% CI = 44%, 95%) and 78% (95% CI = 42%, 91%), respectively, of the reduction in perinatal deaths from Rh disease. Similar results were obtained with conditional probability modeling, which also provided estimates for the effects of changes in abortion rates and racial composition. CONCLUSIONS: In addition to Rh prophylaxis, changes in other determinants were responsible for an important fraction of the decline in Rh disease. These results provide a historical perspective on the conquest of Rh disease and also have important implications for public health policy, particularly in developing countries.

Erythroblastosis, Fetal↗
PubMed1984

Antenatal prophylaxis of Rh immunization with 250 micrograms anti-D immunoglobulin.

Anti-D immunoglobulin (250 micrograms) was given i.m. to 830 Rh-negative primigravidae and multigravidae round the 32nd to 34th week of gestation. The multigravidae had previously been treated with anti-D immunoglobulin post partum or after abortion and had been followed up serologically after 8 months. Five hundred and twenty-nine of the women delivered Rh-positive infants and received another injection of anti-D immunoglobulin (250 micrograms) within 72 hours of delivery. At the serological follow-up 8 months after delivery 2 women (0.4%) had weak anti-D antibodies by the papain technique. No anti-D could be detected in these 2 women 14 and 20 months, respectively, after delivery. In a previously performed postnatal clinical study with 250 micrograms anti-D immunoglobulin the failure rate was 1.6% (10 out of 645 women). Thus, antenatal prophylaxis significantly (p less than 0.05) reduced the incidence of Rh immunization. The haemoglobin and bilirubin levels in cord blood and capillary blood did not differ in the Rh-positive and Rh-negative infants. Three primiparae (0.2%) had anti-D antibodies at the time of the antenatal injection before delivery. Thus, the antenatal regimen of gestation did not give full protection from Rh immunization. It is suggested that an antenatal injection at the 28th week of gestation would have been more effective, as Rh sensitization during pregnancy has been reported to be more frequent from the 29th week of pregnancy. Since the introduction of postnatal anti-D prophylaxis the Rh immunization occurring during pregnancy accounts for most of the observed failures (2, 4, 5, 14, 20). The efficacy and safety of antenatal injection of anti-D immunoglobulin has therefore been investigated (5, 6, 7). At the Växjö Hospital in Sweden, where the incidence of anti-D antibodies was 1.6% (15), 250 micrograms of anti-D immunoglobulin were given at about 32-34 weeks of gestation from March, 1973, to December, 1977. The results are presented here.

Antibodies↗
PubMed1985

Intensive plasma exchange as an adjunct to management of severe rhesus disease.

Large-volume plasma exchange was used to reduce the maternal anti-D concentration in a case of severe rhesus disease. The treatment commenced at 19 weeks' gestation and continued until the infant was successfully delivered at 35.2 weeks' gestation. The initial anti-D level of 30 IU/ml was lowered to 10 and was maintained below that level, with few exceptions throughout the program. The volume of plasma exchanged each week varied between 6.8 and 13.4 liters, a total of 154 l. Three IUTs were accomplished, starting from 31 weeks' gestation. The patient's OD values remained far below those recorded in her previous pregnancy which terminated in neonatal death. The replacement fluids consisted of 98 l PPS with FFP added to equilibrate the patient at the end of each procedure, altogether 33 l. At 33 weeks' gestation she developed a transient non-A, non-B hepatitis probably caused by the use of FFP. However, she later made a complete recovery. Large-volume plasma exchanges commenced early in high-risk pregnancy must be individually designed and based on the kinetics of anti-D production. The replacement fluids should preferably consist of pasteurized albumin solutions and intravenous immune globulin.

Adult↗
PubMed1992

Allo-immunization during pregnancy. Clinical results from 1983 to 1989 in a Scandinavian university hospital.

From 1983 to 1989, 147,068 pregnancies were analyzed for allo-immunization against erythrocyte antigens. Approximately half of the cases were due to immunization against factor D and the others were due to allo-immunization against other antigens (K, c, E, etc.). In 61 cases exchange transfusion of the newborn was needed and in 115 cases diagnostic amniocentesis was done during pregnancy. Intrauterine transfusions were performed in 10 cases. Fetal and neonatal mortality was 4% in these moderate to severe cases, all due to immunization against D. Immunization against D was due to failure to give immunoglobulin anti-D in about 2/3 of the cases. Systematic prophylactic treatment with anti-D during pregnancy would probably not be cost-effective in this population.

Amniocentesis↗
PubMed1993

Evaluation of a new Swedish protocol for alloimmunization screening during pregnancy.

Screening protocols for alloimmunization during pregnancy usually make a difference between primi- and multigravidae as well as between Rh(D) negative and Rh(D) positive pregnant women. We have evaluated a new screening program including antibody tests at 25 and 35 gestational weeks only, for all, and regardless of Rh(D) group. During the time period 1983-89, 78,300 consecutive pregnancies were tested. Red cell antibody immunizations were detected in 287 (0.37%) pregnancies subdivided into fourteen different red cell IgG antibody specificities. Significant antibody titers (defined as IAT or enzyme titers > or = 8) were observed in 225 pregnancies, where 127 (56%) were previously unknown. A majority (63%) of the new immunizations occurred among the Rh(D) positive pregnant women. All newborns that needed phototherapy or exchange transfusion due to alloimmunization were recognized at the time of delivery. We conclude that antibody screening tests at 25 and 35 gestational weeks for both Rh(D) negative and positive pregnant women is sufficient, effective and a safe procedure for the fetus as well as for the mother.

Coombs Test↗
PubMed1997

Concentration of anti-D antibodies in Rh(D) alloimmunized pregnant women, as a predictor of anemia and/or hyperbilirubinemia in their newborn infants.

OBJECTIVES: To define a simple, safe and reliable program for the monitoring of anti-D alloimmunized pregnancies by analysis of the covariation between antenatal values of the titer and the concentration of anti-D antibodies in maternal serum, the deltaOD(450 nm) in amniotic fluid samples, and the levels of B-hemoglobin and S-bilirubin in the newborns at birth. SUBJECTS: Ninety-three Rh(D) negative women with anti-D antibody titers > or = 16 who, after the completed 34th gestational week, gave birth to Rh(D) positive babies with a positive direct antiglobulin test. METHODS: The titers and the concentrations of anti-D antibodies in maternal serum were determined by standard procedures every second week from the 25th week of gestation. In 47 of the 93 women, deltaOD(450 nm) in amniotic fluid was determined at least once. All antenatal values used in the study were determined within 14 days before delivery. RESULTS AND CONCLUSION: Maternal serum antibody titers < or = 32 or > or = 1000 could in themselves well predict unaffected and affected newborns. Antibody titers between 64 and 512 could not accurately predict newborns with or without hemolytic disease. As a complementary monitoring test, determination of the deltaOD(450 nm) was found to be less accurate when compared to determination of the concentration of anti-D antibodies. In order to monitor Rh(D) alloimmunized pregnancies, determination of the concentration of anti-D antibodies may possibly replace determination of deltaOD(450 nm).

Amniotic Fluid↗
PubMed1999

Fetal RhD genotyping from maternal plasma.

The prenatal diagnosis of fetal rhesus D (RhD) status is useful for the management of RhD-negative women with partners heterozygous for the RHD gene. Conventional methods for prenatal fetal RhD status determination involve invasive procedures such as fetal blood sampling and amniocentesis. The recent demonstration of the existence of cell-free fetal DNA in maternal plasma and serum opens up the possibility of determining fetal RhD status by analysis of maternal plasma or serum DNA. This possibility has recently been realized by three independent groups of investigators. This development represents an important step towards the routine application of noninvasive fetal blood group diagnosis in sensitized pregnancies and may become a model for developing safer noninvasive prenatal tests for other single-gene disorders.

Blood Grouping and Crossmatching↗