Hemolytic Disease Of Fetus And Newborn Research Articles

EE243 Utilization of Healthcare Resources and Costs of Hemolytic Disease of Fetus and Newborn (HDFN) in Israel

EE243 Utilization of Healthcare Resources and Costs of Hemolytic Disease of Fetus and Newborn (HDFN) in Israel

Racial Disparity in Antibody Against High Prevalence Antigen; Anti-U

Abstract Introduction/Objective Anti-U is an IgG antibody directed against the U antigen, which usually forms after exposure to U antigen via blood transfusion and/or pregnancy. U antigen is located on glycophorin B (GYPB) as part of the MNS blood group system. Approximately 2% of the African American population lacks this antigen, making them prone to developing anti-U. Anti-U can cause hemolytic disease of fetus and newborn (HDFN) and hemolytic transfusion reactions (HTR). Methods/Case Report A 60-year-old African American male underwent aortic valve surgery. The patient was A Pos with a negative antibody screen. During surgery, the patient was transfused with 3 random units of packed red blood cells (PRBCs). The postoperative course was uncomplicated, and the patient was discharged home. 6 months later, the patient was admitted for another procedure and was expected to require blood products. Thus, a type and screen test was ordered, revealing pan reactivity on screening cells. This prompted further investigation. Antibody detection was performed with the solid-phase technique followed by the tube method with Polyethylene glycol (PEG) as an enhancement medium. PEG technique is the next choice of method if the solid phase requires extended antibody work up, which was the case in our patient. PEG tube method successfully identified Anti-U, and the patient's phenotype was confirmed to be U negative. Results (if a Case Study enter NA) N/A. Conclusion It is imperative to stress the importance of racial disparity while investigating antibodies against high prevalence. In our case, our suspicion was high for Anti-U, given that patient was of African American descent. Tube methods with PEG and Solid Phase techniques are usually used for antibody identification. It is recommended that patients with rare antibodies carry an Antibody ID card indicating the rare antibody they have to prevent further exposure.

ABO and Rh Antigen Distribution Among Pregnant Women in South Western Uganda.

IntroductionABO and Rh are the major blood group systems in Transfusion Medicine, the ABO system based on two red cell antigens (A, B) while the Rh has about 50 antigens of which five are highly clinically significant (D, C, c, E, e). These vary among races and ethnic groups. Blood type phenotype incompatibility between mother and fetus may result in antigen mismatch, triggering alloimmunization, and thus causing hemolytic transfusion reaction (HTR), which results in hemolytic disease of fetus and newborn (HDFN). This study aimed to determine the frequencies of ABO and rhesus blood group antigen in the pregnant women in South Western Uganda.MethodsA cross-sectional study was carried out on 1369 pregnant women who were recruited and provided consent to participate during their regular antenatal visits between August 2020 and July 2021. Four milliliters (4mL) of EDTA-anti-coagulated blood samples were collected and ABO and Rh-blood grouping including Rh antigen screening was done using the agglutination technology comprised of glass beads and reagent contained in a column of the Ortho Biovue ID Micro Typing System (Ortho Clinical Diagnostics, New Jersey, USA). The Rh antigen phenotypes and frequencies were then determined.ResultsThere was percentage distribution of 99.8%, c 99.3%, D 94.3%, C 19.2% and E 15.9%, with Rh cDe/cDe (65.1%) being the most common phenotype followed by cDe/CDe (15%), cDe/cDE (10.8%) and cDE/cDE 0.1% least common. The ABO grouping frequency was obtained as O 49.4%, A 29.5%, B 17.0% and AB 4.1%, with D positivity at 94.3%.DiscussionPopulation genetic variations result in varied expressions of red cell antigens that may have clinical complications. Knowledge of the presence of these Rh antigen distributions and phenotype frequencies during pregnancy help in rational management of the pregnancy, alloimmunization and better approach to safe blood transfusion.

Prevalence of Rhesus & Kell phenotypes among blood donors of Bangladesh

The Rhesus blood group system is one of the most polymorphic and highly immunogenic systems in humans. Because of its high and strong immunogenicity Rh D antigen testing is mandatory before issuing a compatible blood. There are five major antigens i.e. DCEce in the Rhesus (Rh) blood group system. On the other hand from the immunogenicity point of view Kell antigen is next to the Rh system. Both of them may cause severe hemolytic transfusion reaction and hemolytic disease of fetus and new born. Exposure of Rhesus negative individuals to Rhesus positive blood through transfusion or pregnancy is most likely to stimulate production of Rhesus antibodies. These antibodies may cause Hemolytic Disease of Fetus and Newborn (HDFN) and Delayed Hemolytic Transfusion Reaction (DHTR). Like Rhesus antibodies, Kell antibodies may also cause HDFN and DHTR. So far we know, there is not enough study regarding antigens C, c, E & e of Rh or K, k antigen of Kell blood group system regarding these antigens in the donors in Bangladesh, thereby exposing transfused patients to these antigens negative patients. To determine the phenotype prevalence of the Rh and Kell blood group systems in the blood donors in Bangladesh, a descriptive cross sectional study was done in the laboratory of Department of Transfusion Medicine, Bangabandhu Sheikh Mujib Medical University, during the period of 1st January 2020 to 31 December 2020. Rhesus Phenotype CCDee is highest (48.4%) & CCDEe & ccDEE both are lowest (0.4%). Most probable Rhesus Genotype CDe/CDe (R1R1) is highest (48.4%) and CDe/CDE (R1Rz) & cDE/cDE (R2R2) both are lowest (0.4%). Kell Genotype kk is highest (99.2%) and Kk is lowest (0.8%). BSMMU J 2021; 14(3): 38-42

Prognostic Significance and Prevalence of IgG Subtypes in Rh Haemolytic Disease of Fetus and Newborn

Many authors have reported poor prognostic value of anti-D antibody titer in the setting of Hemolytic Disease of Fetus and Newborn (HDFN). According to literature, HDFN cases with IgG1 and IgG3 have more severity compared to IgG2 and IgG4.Therefore, we planned this study to evaluate the prevalence and prognostic value of IgG subtypes in the setting of Rh HDFN. This was a retrospective study performed at a tertiary care center in north India from October 2015 to November 2017. Women with anti-D antibody were included in the study and categorized on the basis of presence of specific IgG subtype. "DAT IgG1/IgG3 ID" card (BIO-RAD) was used for determining the subclass of IgG. Various clinical, laboratory & interventional parameters were used to categorize fetal outcome in severe and non-severe cases. Perinatal outcome was then compared between women with different IgG subclass profile. Subclass distribution among 80 alloimmunized women was 26.2% for IgG1, 15% for IgG3, 46.2% for IgG1 + IgG3 and the rest had neither IgG1 nor IgG3. Severity of HDFN was significantly higher when IgG1 &/or IgG3 were present alone or in combination, compared to cases with absence of IgG1 or IgG3 (p value < 0.05). Risk of severe HDFN was significantly higher in the presence of IgG1 &/or IgG3 and the severity was highest when both IgG1 and IgG3 were present. We recommend that IgG subclass determination should be included in a multi-parameter protocol for more accurate prediction HDFN severity to ensure timely referral and intervention.

Non-Invasive Prenatal Fetal Blood Group Genotype and Its Application in the Management of Hemolytic Disease of Fetus and Newborn: Systematic Review and Meta-Analysis.

Hemolytic disease of fetus and newborn (HDFN) imposes great healthcare burden being associated with maternal alloimmunization against parental-inherited fetal red blood cell antigens causing fetal anemia or death. Noninvasive prenatal analysis (NIPT) provides safe fetal RHD genotyping for early identification of risk pregnancies and proper management guidance. We aimed to conduct systematic review and meta-analysis on NIPT's beneficial application, in conjunction with quantitative maternal alloantibody analysis, for early diagnosis of pregnancies at risk. Search for relevant articles was done in; PubMed/Medline, Scopus, and Ovid (January 2006April 2020), including only English-written articles reporting reference tests and accuracy data. Nineteen eligible studies were critically appraised. NIPT was estimated highly sensitive/specific for fetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons are optimum to increase accuracy. NIPT permits cost-effectiveness, precious resources sparing, and low emotional stress. Knowledge of parental ethnicity is important for correct NIPT result interpretations and quantitative screening. Cut-off titer ≥8-up-to-32 is relevant for anti-D alloantibodies, while, lower titer is for anti-K. Alloimmunization is influenced by maternal RHD status, gravida status, and history of adverse obstetrics. In conclusion, NIPT allows evidence-based provision of routine anti-D immunoprophylaxis and estimates potential fetal risks for guiding further interventions. Future large-scale studies investigating NIPT's non-RHD genotyping within different ethnic groups and in presence of clinically significant alloantibodies are needed.

Non RhD isoimmunization causing severe hemolytic disease of fetus and newborn in Rh positive pregnancies: report of 2 cases with review of literature

Anti D immunoprophylaxis widespread use in antenatal patients has led to dramatic reduction in the rates of alloimmunization due to anti D, which is the most common Rh antibody causing severe Hemolytic Disease of Fetus and New born (HDFN). However, there has been increase in the rates of non Rh D antibodies causing alloimmunization in pregnant women and leading to moderate to severe HDFN. We hereby report two cases of neonates presenting with moderate to severe HDFN with strongly positive DAT due to Rh anti-c antibody in Rh-positive mothers. Thus, antenatal antibody screening should be done in all Rh-positive pregnant women to prevent the diagnostic delay of HDFN occurring due to Non anti-D isoimmunization in the fetus.

A rare case of immune hydrops in an “Elevated D” pregnancy

The D-/-phenotype is a rare variant of the Rh system, in which red blood cells express only D antigen. Sensitized D-/-women carry a risk of hemolytic disease of fetus and newborn (HDFN) and pose a challenge in management due to nonavailability of antigen negative blood for intra-uterine/exchange-transfusion. A 23y old G2P1L1A0, blood group “A” Rh D+C-c-E-e- presented at 20 weeks' period of gestation (POG) with a positive indirect antiglobulin test. Cordocentesis at 23 weeks' POG revealed fetal's blood group as “B” Rh D+, Direct Coombs Test 4+, Hemoglobin 2.8 g/dL. USG with MCA-PSV indicated rapid development of fetal anemia and hydrops. Patient's sibling had D-/-phenotype, but was ABO-incompatible with the fetus. Rapidity of progression of case resulted in intrauterine fetal demise at 27 weeks' POG. HDFN, in rare blood groups, leads to problems in arranging compatible units in developing countries due to lack of centralized rare donor registries.

Hemolytic disease of newborn caused by multiple Rh antibodies

Hemolytic disease of Fetus and Newborn (HDFN) usually results due to natural occurring antibodies or alloimmunization in mother but the presence of multiple red cell antibodies increases the risk of development of significant HDFN. Here author reported a case of hemolytic disease of fetus and newborn in a preterm baby caused by multiple maternal antibodies. Direct Antiglobulin Test (DAT) on neonate blood sample was positive (3+) with monospecific DAT showed IgG type which was confirmed by heat elution. Antibody identification of eluate was done using commercial 11-cell panel by gel method showing specificity to anti-D and anti-C antibody which was differentiated from anti-G by sequential adsorption and elution studies. Neonate was treated with double volume exchange transfusion (DVET) using leucoreduced, irradiated O Rh D and C negative PRBC suspended in AB plasma and discharged 6th day in a stable condition. So, all pregnant women should be at least advised for ICT irrespective of Rh D negative status. If ICT is positive, they should be referred to higher center for proper Immunohematological work up, so that proper blood unit for DVET could be identified.

Blocked-D phenomenon in hemolytic disease of fetus and newborn with multiple maternal antirhesus antibodies

Background: The blocking of D antigen sites of RBC membrane of the fetus by the passively transferred IgG anti-D in cases of Hemolytic Disease of fetus and new born (HDFN) is called blocked- D phenomenon. The coating of maternal IgG type of anti-D prevents the agglutination of the Rh-(D) antigen positive red blood cells (RBC) by the IgM D-antigen typing reagents. We are reporting two cases of Rh-(D) HDFN which were falsely typed as Rh (D) antigen negative with routine typing reagents and had multiple allo-antibodies in the maternal serum. Aims: To rule out HDFN and to confirm the Rh-(D) status of baby, to detect the presence of other allo-antibodies in the maternal serum that can complicate future transfusions in mother. Materials: After routine blood grouping, sample of baby was subjected to adsorption-elution studies and maternal serum was used for antibody screening and identification Results: In both the cases, blocked-D phenomenon got detected and there were multiple anti-rhesus antibodies other than anti-D in the maternal serum. Conclusion: Antibody identification in antenatal women is important in the case management of HDFN to protect future pregnancies and to avoid the risk of mismatched transfusions.

PROPORTION OF RHESUS BLOOD TYPE PHENOTYPES OF ROUTINE BLOOD DONORS AT BLOOD DONOR UNIT INDONESIAN RED CROSS IN BANDUNG CITY

Blood type phenotype incompatibility including Rhesus between donors and patients may result in cross-matching problems, triggering alloimmunization, and caused Hemolytic Transfusion Reaction (HTR). Rhesus blood type incompatibility between mother and fetus may cause Hemolytic Disease of Fetus and Newborn (HDFN). Pretransfusion phenotypic blood groups matching also reduce cost efficiently which means antibody screening is no longer needed. The purpose of the study is to find the proportion Rhesus blood type phenotypes in routine blood donors at Blood Donor Unit, Indonesian Red Cross in Bandung city, Indonesia.The study is a descriptive and observational with cross sectional design. The study was done at Blood Donor Unit, Indonesian Red Cross in Bandung city from April 2016 to September 2017. The subjects were 142 routine blood donors, blood sampling was done simultaneously with blood donation. Rhesus antigen examination of ethylenediaminetetraacetic acid (EDTA) blood was done by gel method. Subjects characteristics were male (68%) and female (32%), with the mean age was 39 years. Examination of Rhesus antigen were found antigen D(100%), antigen e(98,6%), antigen C(97,9%), antigen c(38,7%) and antigen E(31,7%). Results of Rhesus phenotypes were DCe/DCe(61,3%), DCe/DcE(29,6%), DCe/dce(7%), DcE/DcE(1,4%) and DcE/dce(0.7%). The distribution of Rhesus blood type were affected by factors such as genetics, race, ethnicity, marriage, demography, and migration. Rhesus blood phenotypes proportion in routine blood donors at Blood Donor Unit, Indonesian Red Cross in Bandung city sorted from the most are DCe/DCe, DCe/DcE, DCe/dce, DcE/DcE and DcE/dce.Keywords: blood donor, phenotype, Rhesus

Kell alloimmunization in pregnancy: Lessons to be learnt

With the introduction of anti-D prophylaxis, the incidence of RhD alloimmunization in pregnancy has been significantly reduced. RhD remains the most common cause of hemolytic disease of fetus and newborn (HDFN). Next to anti-D, anti-K and anti-c have been implicated in severe HDFN. Hereby, we report a case of Kell alloimmunization in pregnancy which is a leading cause of HDFN worldwide. This case highlights the need for tertiary care hospitals to establish a well-defined protocol for the management of Kell alloimmunization in antenatal females. Most commonly, Kell alloimmunization is secondary to previous transfusions, and hence, every attempt should be made for primary prevention, i.e., Rh-Kell-matched transfusions for women of reproductive age group.

Quantitative fetomaternal hemorrhage assessment with the use of five laboratory tests.

In various countries, standard doses of anti-D IgG used for postpartum immunoprophylaxis of hemolytic disease of fetus and newborn (HDFN) vary from 100 μg to 300 μg. There are also different regulations concerning FMH assessment, and opinions about applicable tests are inconclusive. Three flow cytometry tests (FCTs) with anti-D, anti-HbF, anti-HbF+CA antibodies, and two modifications of microscopic Kleihauer-Betke test (KBT) were used. In all artificial mixtures with known concentrations, FCTs and KBT with counting 10 000 RBCs had similar satisfying sensitivity and specificity. KBT with counting 2000 RBCs had to be disqualified because of significant discrepancies between expected and measured values of FMH. The test procedure with anti-D was easier and shorter than the remaining tests, but it can be only used for FMH assessment in RhD-negative mothers with RhD-positive newborns. In one clinical sample, it was impossible to distinguish fetal RBCs from maternal F cells in KBT and FC with anti-HbF but other tests were useful. In the four tests, correlation between expected and obtained results was appropriate (CCC ̴1). Each test had some advantage and limitation in any clinical situation. Therefore, it is best to have opportunity to perform two or three assays in the laboratory.

Correlation between the Amount of Anti-D Antibodies and IgG Subclasses with Severity of Haemolytic Disease of Foetus and Newborn.

AIM:The aim of this study was to investigate the influence of subclasses to IgG anti-D on the intensity of hemolytic disease of fetus and newborn (HDFN) at 45 fetuses/newborns with symptoms of mild and severe HDFN in Republic of Macedonia.MATERIAL AND METHODS:In retrospective and prospective studies, in a period of 10 years, from 2004 to 2014, there have been immunohemathology tests performed on 22 009 samples on serums of pregnant women.RESULTS:At 37.78% of the total number of tested patients, IgG1 and IgG3 was the reason for severe HDFN. At 17.77% of the total number of tested patients, which had only IgG1detected, was the reason for serious intensity of HDFN. The correlation of the titer to anti-D antibodies in the mother’s serum and the intensity of HDFN were researched in 48 newborns. The titers between 1:8 and 1:32 resulted in 3 cases of HDFN with symptoms of severe disease and in 4 cases there were no signs of HDFN. At 12 women that had a titre between 1:32 and 1:512, five of the newborns developed severe HDFN, and seven had symptoms of mild and weak intensity form. In 3 cases the titer was higher than 512, and out of them one newborn had weak symptoms of HDFN, one developed severe HDFN and one ended with foetal death. Only in one case the titer reached a value higher than 1000, and it ended with a fetal death.CONCLUSIONS:The titers of the pregnant women serum those are lower than 32 and those higher than 1000 can well predict HDFN. The titers of anti-D antibodies between 64 and 512 have no exact predictive value. IgG1 and IgG3 subclasses of anti-D have no predictive value by themselves, and cannot foresee the outcome of HDFN. The research study results suggest that IgG1 and IgG3 should be included in a multi – parameter protocol for evaluation of the HDFN intensity. They can give a real assessment of the expected HDFN intensity in combination with the titer hight and the significance of the antibodies.

Syncytial nuclear aggregates and villous capillary volume in IUGR placentas: A stereology-based study on virtual slides

Hemolytic disease of fetus and newborn (HDFN) imposes great healthcare burden being associated with maternal alloimmunization against parental-inherited fetal red blood cell antigens causing fetal anemia or death. Noninvasive prenatal analysis (NIPT) provides safe fetal RHD genotyping for early identification of risk pregnancies and proper management guidance. We aimed to conduct systematic review and meta-analysis on NIPT's beneficial application, in conjunction with quantitative maternal alloantibody analysis, for early diagnosis of pregnancies at risk. Search for relevant articles was done in; PubMed/Medline, Scopus, and Ovid (January 2006April 2020), including only English-written articles reporting reference tests and accuracy data. Nineteen eligible studies were critically appraised. NIPT was estimated highly sensitive/specific for fetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons are optimum to increase accuracy. NIPT permits cost-effectiveness, precious resources sparing, and low emotional stress. Knowledge of parental ethnicity is important for correct NIPT result interpretations and quantitative screening. Cut-off titer ≥8-up-to-32 is relevant for anti-D alloantibodies, while, lower titer is for anti-K. Alloimmunization is influenced by maternal RHD status, gravida status, and history of adverse obstetrics. In conclusion, NIPT allows evidence-based provision of routine anti-D immunoprophylaxis and estimates potential fetal risks for guiding further interventions. Future large-scale studies investigating NIPT's non-RHD genotyping within different ethnic groups and in presence of clinically significant alloantibodies are needed.

Hemolytic disease of fetus and newborn due to maternal red blood cell alloantibodies in the Malay population.

Background:Maternal red blood cell (RBC) alloimmunization may lead to production of harmful antibodies that result in hemolytic disease of fetus and newborn (HDFN). There is insufficient data on the prevalence of HDFN due to RBC alloantibodies in the Malay neonatal population.Aim:The aim of this study was to determine the incidence of HDFN in the Malay neonatal population due to clinically significant RBC alloantibodies.Subjects and Methods:A cross sectional study was conducted in Transfusion Medicine Unit, Hospital Universitiy Sains Malaysia over one year period from January to December 2009. A total of 5163 Malay pregnant women who attended labor room for delivery were collected and analyzed prospectively. The blood samples were subjected to the standard immunohematological procedure for RBC antibody screening and identification using reagents of Diamed-ID Gel microtyping system. All the newborns with RBC alloantibody were investigated for the evidence of HDFN.Results:Thirty (0.58%) women were found to have clinically significant RBC alloantibodies. Most of the alloantibodies belonged to Rhesus (Rh) system (56.7%) where anti-E (33.3%) was the most common followed by anti-D (10.0%). Rh antibodies were the main cause of HDFN in fourteen (0.27%) neonates. Anti-D and anti-c were identified to cause moderate to very severe HDFN.Conclusions:With the low prevalence of clinically significant RBC alloantibodies and HDFN, routine antenatal antibody screening practice may not be advised as a routine practice at present, preferably reserved for those women of RhD negative or with history of HDFN, significantly of those attributed to anti-c.

Rhesus-D zygosity and hemolytic disease of fetus and newborn

Alloimmunization against the Rhesus-D (RhD) antigen still remains as a major cause of hemolytic disease of fetus and newborn (HDFN). Determination of paternal RhDzygosity is performed by molecular testing and is valuable for the management of alloimmunized pregnant women. A 30-year-old pregnant woman with AB negative blood group presented with two consecutive abortions and no history of blood transfusion. By application of the antibody screening, identification panel, and selected cells, she was found to be highly alloimmunized. RhDzygosity was performed on her partner and was shown to be homozygous for RhD. The sequence- specific priming-polymerase chain reaction used in this report is essential to establish whether the mother requires an appropriate immunoprophylaxis or the fetus is at risk of HDFN.

Absence of hemolytic disease of fetus and newborn (HDFN) in a pregnancy with anti-Yka (York) red cell antibody

Abstract The York antigen, assigned to the Knops system (KN5-ISBT 022005), is a high frequency antigen present in 90% of the Caucasian and 98% of the African-American population. No cases of anti-Yka in pregnancies have been published. No hemolytic diseases of the fetus and newborn have been observed previously. We report the first case of anti-Yka antibody found in a pregnant woman without fetal anemia, which was monitored by Doppler assessment of peak systolic velocity at the middle cerebral artery. A 36-year-old white woman, gravida 2, para 2 (1994 and 1996) was transfused with two units of packed red cells in 2009. On July 1, 2011 at 13 weeks of gestation of her third pregnancy, “type and screen” showed blood group 0 RhD positive and was found to have one IgG antibody that reacted against all panel red blood cells in the anti-human globulin phase by gel technique. The antibody was identified as anti-Yka and titer was 64. The patient’s phenotype was YK(a–). Peak systolic velocity at the middle cerebral artery, performed by Doppler, at weeks 25, 28, 32 and 34 of gestation did not show fetal anemia. At birth, the newborn was group 0 Rh (D) positive, Yk(a+) with direct Coombs test negative without anemia and hyperbilirubinemia. Our case contributes, as further evidence, to the clinically benignity of the anti-Yka antibody not been a cause of hemolytic disease of the fetus and newborn.

Severe hemolytic disease of fetus and newborn caused by red blood cell antibodies undetected at first‐trimester screening (CME)

The objective was to determine clinical consequences of anti-D and non-D antibodies undetected at first-trimester screening for infant or fetus. This retrospective cohort study included all pregnant women with red blood cell (RBC) antibodies who were tested between 1993 and 2008. Data were obtained from the forms for tracking immunization at the transfusion department. Each form was analyzed for three data sets: the order of screening at which the antibodies were detected (initial or repeated screening), the order of pregnancy (first pregnancy or higher), and whether the antibodies caused severe hemolytic disease of fetus and newborn (HDFN). In D- women, anti-D was detected in 1.3% of cases. The anti-D was undetected in 72 (37%) cases on the first-trimester screening, of which eight cases were complicated by severe HDFN. In this group, three patients were primigravidae. An overall non-D incidence of 0.2% was observed. In 16 cases, non-D were undetected on the first-trimester screening (10 anti-c, two anti-E, two anti-C, one anti-S, and one case of anti-Rh17). Non-D antibodies undetected on initial screening caused 11 cases of severe HDFN (27% of all severe non-D HDFN). Ten of them were in multiparous women. Seven of 11 cases with severe HDFN that were missed were caused by anti-c. The third-trimester screening may detect RBC antibodies that were not present or detected on the first-trimester screening. Such screening may be especially relevant in D+ multiparous women due to the risk of HDFN.

Prévention de l'allo-immunisation Rhésus-D fœto-maternelleRecommandations pour la pratique clinique élaborées par le Collège national des gynécologues et obstétriciens français

Hemolytic disease of fetus and newborn (HDFN) imposes great healthcare burden being associated with maternal alloimmunization against parental-inherited fetal red blood cell antigens causing fetal anemia or death. Noninvasive prenatal analysis (NIPT) provides safe fetal RHD genotyping for early identification of risk pregnancies and proper management guidance. We aimed to conduct systematic review and meta-analysis on NIPT's beneficial application, in conjunction with quantitative maternal alloantibody analysis, for early diagnosis of pregnancies at risk. Search for relevant articles was done in; PubMed/Medline, Scopus, and Ovid (January 2006April 2020), including only English-written articles reporting reference tests and accuracy data. Nineteen eligible studies were critically appraised. NIPT was estimated highly sensitive/specific for fetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons are optimum to increase accuracy. NIPT permits cost-effectiveness, precious resources sparing, and low emotional stress. Knowledge of parental ethnicity is important for correct NIPT result interpretations and quantitative screening. Cut-off titer ≥8-up-to-32 is relevant for anti-D alloantibodies, while, lower titer is for anti-K. Alloimmunization is influenced by maternal RHD status, gravida status, and history of adverse obstetrics. In conclusion, NIPT allows evidence-based provision of routine anti-D immunoprophylaxis and estimates potential fetal risks for guiding further interventions. Future large-scale studies investigating NIPT's non-RHD genotyping within different ethnic groups and in presence of clinically significant alloantibodies are needed.