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The global burden of Rh disease
... There are many advantages associated with this implementation [305,306]. The test is significantly sensitive and specific with diagnostic sensitivity ranging from 95 to 100% and specificities over 99% [307][308][309]. The prevalence of Rh D negative varies widely between Caucasians with a prevalence >14% [307][308][309][310] compared to ethnic groups of sub-Saharan Africa with a prevalence ranging between 2.4 and 4.5% [311]. ...
... The test is significantly sensitive and specific with diagnostic sensitivity ranging from 95 to 100% and specificities over 99% [307][308][309]. The prevalence of Rh D negative varies widely between Caucasians with a prevalence >14% [307][308][309][310] compared to ethnic groups of sub-Saharan Africa with a prevalence ranging between 2.4 and 4.5% [311]. Evidence has shown that 40% of Rhesus D negative women carry D Negative foetuses. ...
The sub-continent of West Africa is made up of 16 countries: Benin, Burkina Faso, Cape Verde, Ghana, Guinea, Guinea-Bissau, Ivory Coast, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, The Gambia and Togo. As of 2018, the population of the sub-continent was estimated at about 381 million. The main challenge associated with blood transfusion service delivery across the sub-region concerns adequacy and safety. In this chapter, we highlighted the challenges associated with the delivery of a quality blood transfusion service in countries in the sub-region including: implementation of component therapy rather than whole blood transfusion, effective cold chain management of blood and blood products, alloimmunization prevention, implementation of column agglutination and automation rather than the convention manual tube method in blood transfusion testing, effective management of major haemorrhage, optimization of screening for transfusion transmissible infections, optimizing blood donation, implementation of universal leucodepletion of blood and blood products, effective management of transfusion-dependent patients, pre-operative planning and management of surgical patients, management of Rhesus D negative pregnancy and women with clinically significant alloantibodies, implementation of haemovigilance system, implementation of alternatives to allogenic blood, availability Blood Donation and Transfusion 2 and use of specialized blood products, optimizing safe blood donation, enhancing blood transfusion safety, operating a quality management system-based blood transfusion service and implementation of non-invasive cell-free foetal DNA testing. There is the urgent need for the implementation of evidence-based best practices in blood transfusion service delivery across the sub-region to allow for excellent, safe, adequate and timely blood transfusion service delivery across the sub-region.
... There are many advantages associated with this implementation [305,306]. The test is significantly sensitive and specific with diagnostic sensitivity ranging from 95 to 100% and specificities over 99% [307][308][309]. The prevalence of Rh D negative varies widely between Caucasians with a prevalence >14% [307][308][309][310] compared to ethnic groups of sub-Saharan Africa with a prevalence ranging between 2.4 and 4.5% [311]. ...
... The test is significantly sensitive and specific with diagnostic sensitivity ranging from 95 to 100% and specificities over 99% [307][308][309]. The prevalence of Rh D negative varies widely between Caucasians with a prevalence >14% [307][308][309][310] compared to ethnic groups of sub-Saharan Africa with a prevalence ranging between 2.4 and 4.5% [311]. Evidence has shown that 40% of Rhesus D negative women carry D Negative foetuses. ...
... There are many advantages associated with this implementation [305,306]. The test is significantly sensitive and specific with diagnostic sensitivity ranging from 95 to 100% and specificities over 99% [307][308][309]. The prevalence of Rh D negative varies widely between Caucasians with a prevalence >14% [307][308][309][310] compared to ethnic groups of sub-Saharan Africa with a prevalence ranging between 2.4 and 4.5% [311]. ...
... The test is significantly sensitive and specific with diagnostic sensitivity ranging from 95 to 100% and specificities over 99% [307][308][309]. The prevalence of Rh D negative varies widely between Caucasians with a prevalence >14% [307][308][309][310] compared to ethnic groups of sub-Saharan Africa with a prevalence ranging between 2.4 and 4.5% [311]. Evidence has shown that 40% of Rhesus D negative women carry D Negative foetuses. ...
The sub-continent of West Africa is made up of 16 countries: Benin, Burkina Faso,
Cape Verde, Ghana, Guinea, Guinea-Bissau, Ivory Coast, Liberia, Mali, Mauritania,
Niger, Nigeria, Senegal, Sierra Leone, The Gambia and Togo. As of 2018, the popula�tion of the sub-continent was estimated at about 381 million. The main challenge
associated with blood transfusion service delivery across the sub-region concerns
adequacy and safety. In this chapter, we highlighted the challenges associated with the
delivery of a quality blood transfusion service in countries in the sub-region including:
implementation of component therapy rather than whole blood transfusion, effective
cold chain management of blood and blood products, alloimmunization prevention,
implementation of column agglutination and automation rather than the convention
manual tube method in blood transfusion testing, effective management of major
haemorrhage, optimization of screening for transfusion transmissible infections,
optimizing blood donation, implementation of universal leucodepletion of blood and
blood products, effective management of transfusion-dependent patients, pre-operative planning and management of surgical patients, management of Rhesus D negative pregnancy and women with clinically significant alloantibodies, implementation of haemovigilance system, implementation of alternatives to allogenic blood, availability and use of specialized blood products, optimizing safe blood donation, enhancing
blood transfusion safety, operating a quality management system-based blood transfusion service and implementation of non-invasive cell-free foetal DNA testing. There is the urgent need for the implementation of evidence-based best practices in blood
transfusion service delivery across the sub-region to allow for excellent, safe, adequate
and timely blood transfusion service delivery across the sub-region.
... The choice of intervention depends on the severity of anemia and gestational age of the fetus [2]. In the absence of preventive measures, approximately 14% of susceptible women will develop anti-D antibodies within 6 months after delivery or during subsequent pregnancies [13]. ...
... The questionnaire was designed based on previous similar articles and a literature search [12][13][14][15] using Google Forms, questionnaire link: https://docs.google.com/forms/d/e/1FAIpQLScYo7wnVBibbozXbill3sPGhhuSqxgIUl5UCPzqV8o Buc9iDA/viewform?usp=sharing). ...
Objective. Rh alloimmunization is a condition where antibodies develop against fetal red blood cell antigens; this can lead to severe complications. However, studies on the awareness among pregnant women about this condition remain limited. This cross-sectional study aims to assess the awareness of Rh alloimmunization among pregnant women in the north of Jordan as a preliminary step toward enhancing the quality of healthcare services provided.
Materials and Methods. In this study, a total of 403 pregnant women were enrolled. Data were collected from pregnant women attending antenatal clinics at King Abdullah University Hospital and Princess Badea’a Hospital using a validated questionnaire. The questionnaire covered various aspects including demographics, awareness of blood type, current pregnancy history, anti-D immunoglobulin administration, and knowledge of Rh alloimmunization. Data analysis was conducted using Statistical Package for Social Sciences software, version 26, focusing on the awareness level of the participants and making comparisons between different categories. Kruskal-Wallis and Mann-Whitney U tests were employed to examine potential variations in knowledge scores.
Results. Based on our results, 39.5% of the participants were aware about Rh alloimmunization, its associated complications, and anti-D immunoglobulin. In addition, the analysis revealed a significant association between a higher level of knowledge about Rh alloimmunization and higher educational level, better socioeconomic status, first pregnancy, negative Rh status, exposure to a sensitizing event during pregnancy, history of indirect Coombs test and anti-D immunoglobulin administration (P-values < 0.001).
Conclusions. The study concluded that there was poor knowledge regarding Rh alloimmunization, its associated complications, and anti-D immunoglobulins.
... 3,4 Failure of Rh immunoprophylaxis is a cumulative cascade of inadequate use of Rh immuneprophylaxis after potential sensitizing events and administration of an inadequate dose. Validation of MCA-PSV for detection of fetal anemia and the need for fetal [1][2][3][4] AbstrAct Objective: The aim of the study was to report pregnancy and fetal outcomes of Rhesus (Rh)-negative pregnancy at a tertiary care teaching hospital. Materials and methods: Prospective observational study was carried out on all Rh-negative women over 3 years period. ...
... Rh D-negative phenotype is the most common in individuals of European and North American descent (15-17%), while the prevalence in the regions of Africa and India (3-8%) and lowest in Asia (0.1-0.3%). 2 Prevalence Rh(D) negative in the Indian population is 5%. The incidence of the disease, (EFW) × 0.14) × (Hct target − Hct initial)/Hct transfused] was used to calculate volume of blood to be transfused. ...
Objective
The aim of the study was to report pregnancy and fetal outcomes of Rhesus (Rh)-negative pregnancy at a tertiary care teaching hospital.
Materials and methods
Prospective observational study was carried out on all Rh-negative women over 3 years period. On the basis of the evolution of indirect Coombs test (ICT), titer and middle cerebral artery peak systolic velocity (MCA-PSV) value, women were categorized into five groups. In the group with ICT >1:32 and MCA-PSV >1.5, multiple of median (MOM) or any features of hydrops underwent intrauterine transfusion (IUT). Pregnancy outcomes, neonatal outcomes, and procedure-related adverse events were analyzed.
Results
A total of 496 women were recruited, out of which 411 were non-alloimmunized, and 85 were alloimmunized. Out of 85 alloimmunized pregnancies, 47 fetuses underwent 148 IUT. The overall perinatal mortality was 1/47, while adverse procedure-related complication was nil in fetuses who underwent IUT. In the IUT group without hydropic fetuses, there was no mortality, but 100% of newborns underwent phototherapy, and 30% underwent exchange transfusion, which was better than the previous studies. In the IUT group with hydropic fetuses, one fetus had mortality out of seven has a cumulative perinatal loss rate of 14%. The procedure-related complication rate was 4.7%.
Conclusion
In the absence of fetal hydrops, IUT has a good prognosis with 100% fetus survival in our center. Advancement in neonatal management [concomitant use of phototherapy and intravenous immunoglobulin (IVIG)] of IUT-received fetuses has significantly reduced morbidity related to hemolytic disease of the fetus and newborn (HDFN). Early detection of pregnancy at risk of fetal anemia using ICT titer and MCA-PSV trend and timely management of fetus at risk of anemia using IUT at fetal medicine center leads to a favorable outcome.
How to cite this article
Arora D, Dey M, Singh S, et al. Management of Rh-negative Alloimmunized Pregnancy Optimizing Perinatal Mortality and Morbidity: A Single-center Study. Int J Infertil Fetal Med 2022;13(3):111-115.
... When fetomaternal hemorrhage occurs, ectopic pregnancy, threatened abortion, spontaneous or induced pregnancy termination, invasive intrauterine procedures, blunt abdominal trauma, any antepartum bleeding episode and external cephalic version (2,3) . It was determined that if the prevention with anti-D prophylaxis is not performed during the antepartum and within 72 hours of delivery, approximately 14% of these patients will develop anti-Rh antibodies within six months or during their subsequent pregnancy (4) . Hemolytic disease of the fetus and newborn (HDFN) remains a severe pregnancy complication that continues to be a major cause of adverse perinatal outcomes. ...
... The use of anti-D prophylaxis has led to a decrease in the incidence of Rh alloimmunization in developed countries. About 1.8% of Rh-negative women develop anti-Rh antibodies following only postpartum prophylaxis, and 0.2% of Rh-negative patients develop these antibodies following both antepartum and postpartum prophylaxis (4,6) . However, no immunoprophylaxis has been produced to inhibit non-D alloimmunizations (7) . ...
Abstract
Objective: This study aims to investigate the distribution of antibodies that cause hemolytic disease of the fetus and newborn (HDFN) and compare the clinical outcomes of pregnancies affected by anti-D and anti-D combined with non-D Rh alloimmunization.
Materials and Methods: We retrospectively searched and obtained the perinatal and neonatal data of patients with anti-D antibodies and anti-D combined with non-D Rh antibodies (anti-c,-C,-e,-E, and-Kell) from October 2015 to December 2018 at the University of Health Sciences Turkey, Kanuni Sultan Süleyman Training and Research Hospital. Univariate and multiple logistic regression analyses and adjusted odds ratios with their confidence intervals were used to define independent risk factors for non-D antibody positive.
Results: The severe fetal hydrops rate was significantly higher in the anti-D combined non-D group (3/25, 12%) than in the anti-D group (1/128, 0.08%, p<0.001). The intrauterine transfusion (IUT) requirement in the anti-D combined non-D group (16/25, 64%) tended to be significantly higher than that in the anti-D group (5/128, 7.46%, p<0.001). The incidence of neonatal exchange transfusion, top-up transfusion, and postnatal phototherapy frequency in the anti-D combined non-D group was significantly higher than in the anti-D group.
Conclusion: Anti-D combined with another non-D Rh alloantibody resulted in significantly higher HDFN rates than the anti-D alloimmunized pregnancies. Also, anti-D in association with non-D Rh antibodies resulted in more severe HDFN requiring more invasive treatment procedures, including IUT, neonatal exchange transfusion, or top-up transfusion.
... The frequency of Rh(D)-negative blood types varies markedly across Pakistan with estimates ranging from 5% in Skardu district, Gilgit-Baltistan [16], 5 to 7% in Peshawar, Khyber Pakhtunkhwa province [17], 6 to 8% in Karachi, Sindh province [18,19], and 8% to 20% in Rawalpindi, Islamabad, Safdarabad, Faisalabad, and Gujrat, in Punjab province [20][21][22]. The genetic determinants of the Rh(D) antigen and its variation across populations are well documented [23]. However, participant recruitment and ...
Rhesus (Rh) disease remains a serious problem in low- and middle-income countries. Rh disease prevention requires early identification and prophylactic treatment of Rh(D)-negative women. We evaluated the feasibility of point-of-care identification of Rh(D)-negative women and timely administration of two doses of anti(D) immunoglobulin by lady health visitors in Dadu district, Sindh, Pakistan. Pregnant women were enrolled at two hospitals and followed until 29 days postpartum. Rh(D)-antigen status was determined using the EldonCard2521 test and all Rh(D)-negative point-of-care test results were attempted to be verified using the conventional test tube agglutination method. Rh(D)-negative women were offered two injections of anti(D) immunoglobulin, one at 28 weeks’ gestation and one within 72 hours of delivery. Knowledge pertaining to Rh disease was assessed among participants at study entry and exit, and in a sample of 30 health care providers. All participants (n=1619) had their blood tested with the EldonCard2521, and 279 (17%) women were found to be Rh(D)-negative; however, the conventional test tube method identified one discordant Rh(D)-antigen result. Among 278 Rh(D)-negative women, 254 (91%) and 268 (96%) received their first and second dose of anti(D) immunoglobulin, respectively. The rates of miscarriage (22.1 per 1,000 pregnancies vs. 4.5 per 1,000 pregnancies), stillbirth (33.8 per 1,000 pregnancies vs. 6.7 per 1,000 pregnancies), and neonatal death (35.0 vs. 16.6 per 1,000 live births) were higher among Rh(D)-negative vs. Rh(D)-positive participants. At study enrolment, there was little knowledge pertaining to Rh disease and its consequences among participants and knowledge also varied greatly among health care providers. The high frequency of maternal Rh(D)-negative blood types, high rates of stillbirth, miscarriage, and neonatal death among Rh(D)-negative women and their newborns, and limited and varied knowledge of Rh disease among pregnant women and health care providers, bolsters the need for a wide-scale Rh disease prevention program in Pakistan.
... The developed world has improved perinatal and neonatal care so the prevalence of Rh incompatibility in these countries has decreased to 2.5/100,000 live births. However, the condition in the developing world is still worse and they need a lot of improvement in their perinatal care to overcome 5 this problem. ...
Abstract
Background: Most prevalent cause of fetal anemia is Rh incompatibility between the mother's and the fetus's blood
types, where antibodies from the mother damage the fetus's red blood cells causing fetal hemolytic anemia.
Objective: To compare the Doppler of the middle cerebral artery of the fetus and cord blood hemoglobin to diagnose
fetal anemia among Rh-negative women in the last trimester of pregnancy.
Methodology: This was a cross-sectional study conducted at the Gynecology & Obstetrics Department, Mercy
Teaching Hospital Peshawar, from February 2020 to May 2021. Atotal of 126 Rh-negative blood group women were
included who were in the last trimester of the pregnancy. Ethical approval was obtained from Ethics Committee and
informed written consent was taken from the study participants. Middle cerebral artery Doppler peak systolic velocity
was checked at 28th, 32nd, and 34th week of gestation. If middle cerebral artery Doppler peak systolic velocity
changes were present, then patients were closely monitored and managed appropriately for post-delivery assessment
of cord blood fetal anemia. Apre-designed structured proforma was used to collect patient details.
Results: Mean age of 126 pregnant mothers was 28±7 years, and the mean parity was 4.57±2. The overall frequency
of fetal anemia among Rh-negative women predicted by middle cerebral artery Doppler peak systolic velocity was 59
(46.8%), while anemia on cord blood sampling after delivery was found in 43 (34.1%) of babies. No anemia was
found in 83 (65.8%) study participants. The sensitivity and specificity of middle cerebral artery Doppler were 100%
and 84% respectively.
Conclusion: Middle cerebral artery Doppler can be a simple noninvasive method to detect fetal anemia before the
development of hydrops fetalis with high sensitivity and specificity.
Keywords: Doppler peak systolic velocity, Fetal Anemia, Hydrops fetalis, Middle cerebral artery, Rh-negative
Article Citation: Burki F, Khan AJ, Ullah N, Parveen S, Javed H, Muqarrab K, Ullah I Fazid S. Comparison of Middle Cerebral Artery Doppler and Cord Blood
Hemoglobin in the Diagnosis of Fetal Anemia among Rh-negative Pregnant Women, Pakistan. JSZMC 2022;13(1):3-6.
DOI: https://doi.org/10.47883/jszmc.v13i01.212
... However, the disease burden of RhD alloimmunization remains high globally. 15,16 Publication bias towards reports from high-income countries may underrepresent the ongoing burden of immune hydrops fetalis, given that its prevention is dependent upon access to RhD immunoglobulin. For example, a recent case series of 62 neonates with hydrops fetalis from Turkey reported that 28 cases (45.2%) were immunemediated compared to the incidence of less than 10% reported elsewhere. ...
... Worldwide, the prevalence of Rh disease is estimated to be 276 per 100,000 live births, which is significant considering that an estimated 50% of untreated cases of HDN will either die or develop brain damage due to the disease. In comparison, the prevalence of Rh disease in developed countries has been reduced to 2.5 per 100,000 live births, which can be attributed to higher-quality perinatal-neonatal care [1,2]. Majority of people about 85% are Rh-positive. ...
Rh incompatibility, also known as Rh disease, is defined as a condition that occurs when a woman with Rh-negative blood type is exposed to Rh-positive blood cells, leading to the development of Rh antibodies. The incidence of occurrence is more frequently among those of Caucasian (North American and European) descent (15% to 17%) compared to those of African (4% to 8%) or Asian descent (0.1% to 0.3%). Worldwide, the prevalence of Rh disease is estimated to be 276 per 100,000 live births, which is significant considering that an estimated 50% of untreated cases of haemolytic disease of the neonate (HDN). HDN will either die or develop brain damage due to the disease. The condition is due to: If a Rhesus negative (Rh-) woman is impregnated by a man with Rhesus negative (Rh-) there wouldn't be any problem. If a Rhesus negative woman (Rh-) is impregnated by a man with Rhesus positive (Rh +) and the baby inherited the rhesus positive (Rh +) from the father there will be a problem or when an Rh-negative mother is exposed to the Rh D antigen, the D antigen is perceived as a foreign threat leading to the haemolysis of the fetal erythrocytes, common signs and symptom include; Jaundice, a yellowing of the skin and whites of the eyes, lethargy, heart failure, enlarged organs. It can be prevented and treated by administering an injection of RhoGAM during the second trimester, and 28th week of pregnancy respectively, exchange transfusions either before birth or after delivery. Phototherapy is also another treatment modality which break down excess bilirubin into less toxic substance that the new borns liver can remove.
... Rhesus disease affects 50% of rhesus factor incompatible pregnancies in the world, and the majority of them is reported from South Asia [3,4]. The rate is high in the progressing countries that have fragile healthcare systems and a lack of standard practices for the prevention of the disease in the background [5]. In Pakistan, almost 270,000 women have Rh factor incompatible pregnancies in a year, and of them 234,000 (87%) women did not receive anti-D prophylactic injection due to the limited availability of anti-D injection. ...
Red cell alloimmunization has been estimated to cause more than 100,000 babies’ death worldwide. Factors like physician’s knowledge, anti-D availability, and affordability are associated globally with the prevalence of rhesus disease. The purpose of this study was to find out factors and assess the current practices followed in Pakistan for the prevention of rhesus disease. This cross-sectional study was conducted at the two tertiary care hospitals in Islamabad from January to November 2022. The data was collected from 150 D− women and 30 physicians on a self-designed questionnaire. The British Committee for Standards in Hematology (BCSH) is used to provide practical guidelines to healthcare providers for the management of blood group incompatibilities in pregnancy. We compared the prevention practices followed in Pakistani hospitals with the BCSH guidelines. The antibody status was identified in only 18 (12%) pregnancies in the third trimester and no women received routine antenatal anti-D prophylaxis (RAADP) during pregnancy to prevent complications in pregnancy. The anti-D injection was administered to 33(22%) women when the potentially sensitive event occurred in pregnancy and 143 (95%) mothers received anti-D after the birth of rhesus-positive fetuses. According to physicians, 83% of families ca not afford anti-D injection and 67% believe the anti-D supply is limited in Pakistan. The rhesus-negative women were not receiving the standard prophylactic treatment as mentioned in guidelines and the reasons attributed to non-adherence were the physician’s poor knowledge, the low family income, along with the non-availability and non-affordability of anti-D injections.
... with antenatal prophylaxis. [2,3] The incidence of non-RhD, non-ABO minor blood group alloimmunization is reported to be around 3%-5%. The most commonly implicated minor blood group antigens are the c, K, C, E, e, Duffy, Kell, Kidd, and MNS antigens. ...
Background
Non-Rhesus D antigen non-ABO, minor blood group alloimmunization in pregnant women is being increasingly recognized as a significant contributor to the development of the hemolytic disease of the fetus and newborn (HDFN). We report severe HDFN in a neonate born to an Rh-positive mother with sickle cell disease, following anti-C and anti-S alloimmunization.
Clinical Description
A male baby born to a repeatedly transfused mother with sickle cell disease developed severe jaundice at 22 h of life. The baby was found to have severe anemia and indirect hyperbilirubinemia, but no encephalopathy, hepatosplenomegaly, or features of sepsis.
Management and Outcome
His blood group was O positive and the direct Coombs test was 4+. Minor blood group typing showed the presence of anti-C and anti-S antibodies. The baby improved after receiving a double-volume exchange transfusion with matched blood and phototherapy.
Conclusion
Severe hemolytic disease of the newborn (HDN) may be caused by minor blood group alloimmunization, especially seen in mothers with a history of multiple transfusions. Antenatal screening for alloimmunization in high-risk mothers can ensure timely diagnosis and treatment of HDN and prevent the harmful effects of neonatal hyperbilirubinemia.
... Rhesus allo-antibodies that areassociated with mild HDN include anti-C anti-E and anti-e [16][17].Anti-D, anti-C, anti-E, and anti-e have all been involved in delayed hemolytic transfusion reactions. The prevention of Rhesus D Factor (RhD) alloimmunization in higher income countries remains one of the most important medical accomplishments of the last century [18][19][20]. The prevention program involves the administration of Rh immune globulin (RhIG), both antenatally and post-natally, and remains the gold standard in effective prevention [21][22][23][24]. ...
The aim is this study is to determine the prevalence of Rh c and Du phenotype among pregnant women attending antenatal clinic (ANC) in Bowen University Teaching Hospital Ogbomoso. The prevalence and distribution of Rh C and Du phenotype was determined using 50 blood samples of 50 different pregnant women consecutively recruited pregnant women aged 18-40 years. Samples were tested for Rh C and Du phenotype using the conventional tube agglutination method using Rapid Laboratories (UK) anti C and Du antisera. Out of 50 samples studied, the prevalence of Rh C was 28% (positivity) while Rh Du was 92% (positivity). The prevalence of Rhesus Du antigens was higher in Ogbomoso since 46 out of 50 samples (92%) tested positive for Rhesus Du antigens. In addition, a 28% prevalence (positivity) obtained does not postulate that Rhesus C antigen distribution in pregnant women in Ogbomoso is low. We recommend that all pregnant women in the area be screened for the presence of clinically significant red cell antigens including Rh C and Du blood group antigens on their first antenatal visit.
... When an RhD-negative mother is pregnant with an RhD-positive fetus, she may be exposed to RhD-positive red blood cells (RBCs) from the fetus during an abortion, a delivery, an amniocentesis, and a blood transfusion, and be sensitized to produce anti-D. This antibody can enter the fetal blood circulation through the placenta and bind to the RhD antigen on the fetal RBCs, leading to fetal and neonatal hemolytic disease, which can cause neurological disorders and even death in severe cases (1)(2)(3). ...
Maternal erythrocyte alloimmunization is one of the most important causes of fetal anemia. The standard treatment for anemic fetuses is intrauterine blood transfusion (IUT). However, IUT may have adverse effects, particularly before 20 weeks of gestation. In this report, two women who had previously had severely affected alloimmunized pregnancy developed high titers of anti-D antibodies before 20 weeks of gestation. Ultrasound Doppler showed severe fetal anemia, and intrauterine transfusion was expected to be unavoidable. To prolong pregnancy to a gestation in which intravascular IUT was possible, we used repeated double filtration plasmapheresis (DFPP) as a rescue therapy. The titers of IgG-D, IgG-A, and IgG-B decreased after DFPP treatment. One woman successfully prolonged pregnancy until 20 weeks of gestation. Subsequently, she underwent four cycles of IUTs and delivered at 30 weeks of gestation by emergency cesarean section due to fetal bradycardia during the fifth intrauterine transfusion. The other woman successfully delayed intrauterine transfusion until 26 weeks of gestation. The favorable results of the two patients indicate that DFPP may be an effective and safe treatment modality for RhD immunity in pregnant women. Moreover, DFPP is potentially helpful for reducing the occurrence of ABO hemolytic disease in neonates due to the clearance of IgG-A and IgG-B antibodies (e.g., O pregnant women harbored A/B/AB neonates). However, more clinical trials are needed to verify the results.
... [9][10][11] Without appropriate intervention such as intrauterine fetal transfusion, up to 50% of HDFN results in fetal death or severe brain injury. [12,13] The general paucity of data on the burden of posttransfusion and pregnancy related alloimmunization from the African perspective is due to poor hemovigilance. [6] Some local reports show alloimmunization rates of 3.4%-4.8% ...
BACKGROUND
Maternal alloimmunization is associated with adverse outcomes such as hemolytic disease of the fetus and newborn. At-risk pregnant women include those with previous multiple gestations or multiple blood transfusions. This study aimed to determine the proportions and specificities of irregular maternal alloantibodies among antenatal attendees at a federal teaching hospital in Nigeria. An understanding of the pattern of alloimmunization, associated morbidities, and attendant risk factors will guide improved antenatal/perinatal health planning.
MATERIALS AND METHODS
A hospital-based, cross-sectional survey was conducted among 150 pregnant women. Data on parity, transfusion history, and other clinical details were obtained with an interviewer administered questionnaire. ABO/Rh D blood groups and hemoglobin phenotypes were retrieved from their antenatal records and confirmed during the study. Alloantibody screening and identification and other serological tests were subsequently performed. Association of independent parameters with other variables was tested using Chi-square analysis or Fisher's exact as appropriate. Level of statistical significance was set at 5% confidence ( P = 0.05).
RESULTS
Most of the participants (60%) were in their third trimester, while 9.3% were in first trimester of pregnancy. Ninety-one percent of the participants (90.7%) were blood transfusion naïve. Seven of the participants (4.7%) had positive alloantibody screens, of which two (1.33%) were clinically significant maternal alloantibodies (Anti-D and Anti-Lu b ). No statistically significant association was observed between alloimmunization and variables such as gestational age, parity, hemoglobin phenotype, previous blood transfusions, and Rh D negativity.
CONCLUSIONS
The authors recommend routine alloantibody screening for at risk pregnancies.
... In pregnant women, such antibodies may cross the placenta and cause HDFN [2,4]. Untreated HDFN can cause neonatal mortality in up to 50% of cases [5]. Timely detection of such antibodies in antenatal women is essential for the early and better management of HDFN, and for the transfusion safety of the mother. ...
Objective:
The study was conducted to determine the frequency of alloimmunization to various blood group antibodies in pregnant women, and the risk of hemolytic disease in the fetus and newborn.
Methods:
All antenatal women, irrespective of the period of gestation or obstetric history, were included, whereas those taking anti-D immune-prophylaxis or with a history of blood transfusion were excluded. Antibody screening and identification were performed using a Bio-Rad ID microtyping system.
Results:
Of 2,084 antenatal females, 1,765 were D-antigen positive and 319 D-antigen negative. Sixty-five (3.119%) women alloimmunized. Out of 54 (2.591%) who had sensitized to D-antigen, 11 (0.527%) also sensitized to other antibodies. These 11 alloantibodies identified included: anti-M (n=6; 9.23%), anti-c (n=1; 3.076%), anti-E (n=1; 1.538%), anti-e (n=1; 1.538%), anti-Lewis (a) (n=1; 1.538%), and unspecified antibodies (n=1; 1.538%). Multiple antibodies were seen in four patients that combined: anti-D and anti-C (n=2; 3.076%), anti-e and anti-c (n=1; 1.538%), and anti-D and anti-G (n=1; 1.538%).
Conclusion:
The rate of alloimmunization in D-antigen-negative women was high. Apart from this, the alloimmunization rate in women with bad obstetric history was very high, at 8.1%. In developing countries such as India, universal antenatal antibody screening, though desirable, may not be justified at present, as the cost and infrastructure required would be immense because of the lower alloimmunization rates in RhD antigen-positive women. However, it is necessary to impose properly formulated protocols to screen pregnant women with bad obstetric history.
... Before the introduction of Rhogam, since there was no adequate treatment of serious erythroblastosis fetalis (or RH disease), tens of thousands of newborns with such hemolytic disease died each year, and RH disease also caused brain damage in thousands more [29][30][31][32]. It was a huge problem demanding a solution (high compelling need). ...
Advances in medical technology do not follow a smooth process and are highly variable. Implementation can occasionally be rapid, but often faces varying degrees of resistance resulting at the very least in delayed implementation. Using qualitative comparative analysis, we have evaluated numerous technological advances from the perspective of how they were introduced, implemented, and opposed. Resistance varies from benign - often happening because of inertia or lack of resources to more active forms, including outright opposition using both appropriate and inappropriate methods to resist/delay changes in care. Today, even public health has become politicized, having nothing to do with the underlying science, but having catastrophic results. Two other corroding influences are marketing pressure from the private sector and vested interests in favor of one outcome or another. This also applies to governmental agencies. There are a number of ways in which papers have been buried including putting the thumb on the scale where reviewers can sabotage new ideas. Unless we learn to harness new technologies earlier in their life course and understand how to maneuver around the pillars of obstruction to their implementation, we will not be able to provide medical care at the forefront of technological capabilities.
... The more the TSB rose above 20 mg/dL, the greater chance of developing kernicterus. Although virtually eliminated nowadays in industrialized Western countries, kernicterus due to Rh disease is still rampant in developing countries (18,19). Kernicterus was first reported in Greece in the 1960s in association with another hemolytic condition, G6PD deficiency (20), and continues to be encountered in recent times both in developing countries with a high indigenous G6PD deficiency frequency as well as in countries where G6PD deficiency has been introduced as a result of immigration and population migration (21). ...
... This rate has been estimated to be between 0.3% and 1% of Rh-negative mothers in the USA (7,8). There is not a published estimate for Canada although 15% of child bearing age women are Rh negative (12). ...
Introduction
Rh sensitization occurs when Rh(D)-negative women develop anti-Rh(D) antibodies following exposure through pregnancy or transfusion. Rh disease may cause jaundice, anemia, neurological impairment, and death. It is rare in countries where Rh Immune Globulin (RhIg) is used. Canadian Rh sensitization and disease rates are unknown.
Methods
This survey-based study was conducted using a Canadian Paediatric Surveillance Program questionnaire sent to Canadian paediatricians and paediatric subspecialists to solicit Rh disease cases from May 2016 to June 2018. Paediatricians reported Rh-positive infants ≤ 60 days of age, born to Rh-negative mothers with RhD sensitization.
Results
Sixty-two confirmed cases of infants affected by Rh(D) sensitization were reported across Canada. The median gestational age of neonates was term, age at presentation was 2 hours, and hemoglobin at presentation was 137.5 g/L (33 to 203 g/L). The median peak bilirubin and phototherapy duration were 280 µmol/L (92 to 771 µmol/L), and 124 hours, respectively. Thirty (48%) infants received Intravenous immune globulin (IVIG) (median two doses). Seventeen (27%) received one to three simple transfusions; 10 (16%) required exchange transfusions. Six (10%) infants presented with acute bilirubin encephalopathy, and less than five presented with seizures. Fourteen mothers with affected infants were born outside of Canada.
Discussion
Rh disease continues to exist in Canada. Additional efforts are needed to raise awareness of Rh disease, prevent disease, and minimize sequelae when it does occur. The ongoing global burden of Rh Disease, as well as the possibility of emerging Rh immunoglobulin refusal are among factors that could be taken into consideration in future prevention efforts.
... Albeit it is cheap and easy to detect Rh D factor during pregnancy, the reproductive risk of Rh D negative women in Africa, Asia, or China is three times that of European women [15]. The distribution of Rh D negative varies widely across the world; among Caucasians, its prevalence is greater than 14% [16], whereas among different ethnic groups of sub-Saharan Africa its prevalence ranges between 2.4 and 4.5% [17][18][19][20]. ...
Background
The Rhesus (Rh) blood group system is the next most clinically significant blood group system following the ABO blood group. Rh D-negative women are at risk of alloimmunization following exposure to Rh D-positive blood. The exposure of Rh D-negative women to Rh D-positive fetal blood may cause hemolytic disease of the fetus or new-born due to Rh incompatibility. Knowing Rh blood phenotype has paramount importance to prevent the risk of sensitization and bad obstetric outcome in Rh D-negative women. Despite the aforementioned fact, the distribution of Rh D-negative phenotype of women was not explored in Arba Minch Zuria district, southern Ethiopia. This study was aimed to assess the prevalence of Rh D-negative blood phenotype among reproductive-age women in Arba Minch Zuria district, southern Ethiopia.
Methods and materials
A community-based cross-sectional study was conducted among reproductive-age women in Arba Minch Zuria district, Southern Ethiopia from March to April 2019. Socio-demographic data were collected using an interviewer-administered semi-structured questionnaire and blood phenotype determination was done by laboratory technicians using the slide method principle aseptically and Statistical Package for Social Science (SPSS) version 21 was used for analysis.
Result
The data were collected from 417 study participants with a 98.8% response rate. This study revealed that 2.1%, 1.9%, 1.2%, and 1% of study participants with blood group O, A, B, and AB were Rh D negative, respectively. In this study, the overall prevalence of Rh D negative phenotype was found 6.2% among reproductive-age women in Arba Minch Zuria district, Southern Ethiopia.
Conclusions
This study showed a high prevalence of Rh D negative factor among reproductive-age women in Arba Minch Zuria district. Therefore, counseling of reproductive age women on the importance of Rh D factor status determination would be worthy to avoid the potential risk of sensitization among Rh D negative women in order to prevent hemolytic disease of the fetus and new-born.
... Because safety is a major focus of surgical and perioperative care, preoperatively acquired blood and blood products remain a routine safeguard for patients undergoing major cancer surgeries. Based on demographic data, the prevalence of the rhesus (Rh)-negative population is 15% in North America and Europe, 4.8% to 6% in Nigeria, 6.49% in India, and 0.33% in the Han nationality population in China (1)(2)(3). Scarcity of Rh-negative donors compounds the blood shortage problem for this patient population. Shortages of allogeneic blood supplies may cause delays in cancer surgeries and prolong length of hospital stay (LOHS), resulting in a failure to achieve optimal timing for these procedures and an adverse effect on prognosis. ...
Background:
Shortages of allogeneic blood supplies for rhesus (Rh)-negative patients who are scheduled for major cancer surgeries may cause delays in surgical procedure, resulting in a prolonged length of hospital stay (LOHS). This study investigated the relationship of acute normovolemic hemodilution (ANH) with LOHS in this patient population.
Methods:
Rh-negative patients who underwent major cancer surgeries between January 2015 and April 2020 were included in this retrospective study. The primary outcome was LOHS. The secondary outcomes were length of preoperative stay (LOPS), perioperative laboratory data and allogeneic blood transfusion (ABT), and postoperative adverse events. Furthermore, relationships between these perioperative variables and LOHS were examined by both univariate analyses and multiple linear regression analysis.
Results:
Seventy patients were divided into ANH (n=30) or Control (n=40) group. The two groups were well-matched for baseline data. LOHS, LOPS, perioperative ABT amount, and the overall rate of postoperative adverse events were all significantly lower in the ANH group (P=0.004, P=0.009, P<0.001, P=0.023, respectively). In the ANH group, levels of hemoglobin and hematocrit decreased on postoperative day 1 (P=0.023, P=0.012, respectively). Univariate analyses revealed significant association between LOHS and the following perioperative variables: ANH, body mass index, types of surgery, intraoperative colloids infusion, and perioperative ABT. Multiple linear regression analysis with correction for diagnosis identified ANH, intraoperative colloids infusion, and perioperative ABT as independent predictors.
Conclusions:
ANH was associated with the decreased LOHS in Rh-negative patients undergoing major cancer surgeries.
... 1 Countries with universal access to perinatal health services have virtually eliminated severe hyperbilirubinemia due to Rh disease. 1 However, worldwide, there has been an enormous failure to prevent Rh sensitization and its adverse consequences with extreme hyperbilirubinemia [EHB, total serum/plasma bilirubin (TB) > 25 mg/dL (428 mmol/L)] resulting in neonatal mortality and long-term disabilities. 2,3 Indeed, the burden of the disease is especially high in low and middle-income countries (LMICs). 1,4 Brazil is the largest South American country with an uppermiddle-income economy (http://www.worldbank.org), a population of approximately 208 million, and 3 million births per year. ...
Universal prenatal Rhesus (Rh) screening and prophylaxis with Rh immunoglobulin have been highly effective practices for preventing neonatal morbidities and mortality. However, there has been an enormous failure to prevent Rh sensitization and its adverse consequences worldwide, especially in low- and middle-income countries (LMICs). Brazil is the largest South American country with an upper-middle-income economy, but has regional inequalities in maternal and newborn care and no national or regional reporting about Rh sensitization. We performed a national survey of multi-healthcare professionals using a closed social media group and demonstrated that Rh disease is present in the country with significant knowledge heterogeneity among professionals and regions. Proper education and training across Brazil are needed to fully eradicate the disease and reduce mortality and long-term disabilities related to neonatal hyperbilirubinemia.
... Commonly encountered clinically significant alloantibodies are against antigens in Rh, Kell, Duffy, Kidd and MNS groups [7][8][9]. Although the incidence of HDFN due to alloantibodies to Rh(D) is significantly reduced by Rh immunoglobulin (RhIg) prophylaxis, it still remains a leading cause of severe HDFN world-wide [10,11]. ...
Alloimmunization to non-ABO, red blood cell (RBC) antigens remains one of the most clinically-relevant complexities faced by blood banking practitioners. In the setting of transfusion therapy, these antibodies raise risks for incompatibilities, while for pregnant patients they can mediate deadly forms of hemolytic disease of the fetus and newborn. As such, a thorough understanding of pathways that lead to alloimmunization, as well as the tools used by blood banks to detect alloantibodies, is critical to transfusion practice. In this review, in which alloimmunization in the setting of pregnancy will be emphasized, we will review: 1) the clinical impacts of RBC alloantibodies in the peri-partum period; 2) the current pathophysiologic mechanisms thought to influence non-ABO antigen alloimmunization; 3) the strengths and weaknesses of laboratory tools used in aiding alloimmunization detection; and 4) future directions of the transfusion community related to alloimmunization impacting pregnancy.
Background/Aims
The increasing burden of haemolytic disease of the newborn as a result of Rhesus incompatibility has raised global concern, prompting the need for targeted research to better understand pregnant women's knowledge. This study was carried out to assess knowledge, attitude and perceived dangers of Rhesus incompatibility among pregnant women attending primary healthcare centres in Ogun State, Nigeria.
Methods
This cross-sectional, descriptive study used simple random sampling to select 366 pregnant women attending antenatal clinics at selected centres in Ogun State, Nigeria. Data were collected using a structured questionnaire and analysed descriptively.
Results
More than half of the participants were aware of their blood group (56.8%) and knew how to identify Rhesus positive and Rhesus negative antigens (50.5%). Overall, 61.4% of participants were classed as having good knowledge about Rhesus incompatibility. Almost all of the participants agreed that a Rhesus compatibility test is very important for pregnant women (92.9%), with over three-quarters agreeing that all women should have a maternal-fetal compatibility test, whether recommended or not (76.2%). Over half (56.0%) of the participants were classed as having a positive attitude.
Conclusions
A large proportion of the participants had poor knowledge and a negative attitude regarding Rhesus incompatibility. More education and awareness is needed at antenatal clinics and marital counselling units to ensure women are aware of the risks of Rhesus incompatibility and the benefits of testing.
Implications for practice
Health talks on Rhesus incompatibility should be included in safe motherhood initiatives. The Nigerian government should subsidise the injection used to prevent postpartum issues in Rhesus negative women for affected pregnant mothers attending government hospitals.
Rhesus immune globulin has resulted in a marked decrease in the prevalence of RhD alloimmunization in pregnancy; however, antibody formation to other red cell antigens continues to occur. Evaluation for the presence of anti–red cell antibodies should be routinely undertaken at the first prenatal visit. If anti–red cell antibodies are detected, consideration of a consultation or referral to a maternal–fetal medicine specialist with experience in the monitoring and treatment of these patients is warranted. Cell-free DNA can be used to determine fetal red cell antigen status to determine whether the pregnancy is at risk of complications from the red cell antibodies. First-time sensitized pregnancies are followed up with serial maternal titers, and, when indicated, serial Doppler assessment of the peak systolic velocity in the middle cerebral artery should be initiated by 16 weeks of gestation. When there is a history of an affected fetus or neonate, maternal titers are less predictive of fetal risk; if the fetus is antigen positive, serial peak systolic velocity in the middle cerebral artery measurements should be initiated by 15 weeks of gestation because intraperitoneal intrauterine blood transfusions can be used at this gestation if needed. The mainstay of fetal therapy involves intrauterine transfusion through ultrasound-directed puncture of the umbilical cord with the direct intravascular injection of red cells. A perinatal survival rate exceeding 95% can be expected at experienced centers. Neonatal phototherapy and “top-up” transfusions attributable to suppressed reticulocytosis often are still required for therapy after delivery.
Hemolytic disease of the fetus and newborn (HDFN) can occur when a pregnant woman has antibody directed against an erythrocyte surface antigen expressed by her fetus. This alloimmune disorder is restricted to situations where transplacental transfer of maternal antibody to the fetus occurs, and binds to fetal erythrocytes, and significantly shortens the red cell lifespan. The pathogenesis of HDFN involves maternal sensitization to erythrocyte "non-self" antigens (those she does not express). Exposure of a woman to a non-self-erythrocyte antigen principally occurs through either a blood transfusion or a pregnancy where paternally derived erythrocyte antigens, expressed by her fetus, enter her circulation, and are immunologically recognized as foreign. This review focuses on the genetics, structure, and function of the erythrocyte antigens that are most frequently involved in the pathogenesis of alloimmune HDFN. By providing this information we aim to convey useful insights to clinicians caring for patients with this condition.
The sub-continent of West Africa is made up of 16 countries: Benin, Burkina Faso, Cape Verde, Ghana, Guinea, Guinea-Bissau, Ivory Coast, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, The Gambia and Togo. As of 2018, the population of the sub-continent was estimated at about 381 million. The main challenge associated with blood transfusion service delivery across the sub-region concerns adequacy and safety. In this chapter, we highlighted the challenges associated with the delivery of a quality blood transfusion service in countries in the sub-region including: implementation of component therapy rather than whole blood transfusion, effective cold chain management of blood and blood products, alloimmunization prevention, implementation of column agglutination and automation rather than the convention manual tube method in blood transfusion testing, effective management of major haemorrhage, optimization of screening for transfusion transmissible infections, optimizing blood donation, implementation of universal leucodepletion of blood and blood products, effective management of transfusion-dependent patients, pre-operative planning and management of surgical patients, management of Rhesus D negative pregnancy and women with clinically significant alloantibodies, implementation of haemovigilance system, implementation of alternatives to allogenic blood, availability Blood Donation and Transfusion 2 and use of specialized blood products, optimizing safe blood donation, enhancing blood transfusion safety, operating a quality management system-based blood transfusion service and implementation of non-invasive cell-free foetal DNA testing. There is the urgent need for the implementation of evidence-based best practices in blood transfusion service delivery across the sub-region to allow for excellent, safe, adequate and timely blood transfusion service delivery across the sub-region.
Background:
Whole blood transfusion has been used for resuscitation in trauma patients; however, case reports of whole blood transfusion for obstetric-related hemorrhage are limited. Whole blood transfusion typically is accomplished with low titer O-positive whole blood, and, despite success in trauma, use in persons with childbearing potential is of concern due to risk of alloimmunization.
Case:
We present a case series of patients who received low titer O-positive whole blood for obstetric hemorrhage. One patient was Rh-negative and received immune globulin treatment after whole blood transfusion. All patients survived to hospital discharge. None experienced transfusion-related complications.
Conclusion:
Whole blood can be successfully administered both in and out of the hospital setting, even for obstetric hemorrhage. The benefits of easily administered balanced resuscitation, limited donor exposure, and improved patient outcomes likely outweigh potential alloimmunization, especially in resource-limited settings. Addressing concerns of alloimmunization cannot be accomplished without more research, and we encourage others to investigate using whole blood in this population.
Management of rh alloimmunised pregnancy
Background: Rh incompatibility has been an important cause of severe neonatal hyperbilirubinemia, hydrops fetalis, and stillbirth.
Among those outcomes, neonatal jaundice is the most common problem.
Objective: The study is assessed the prevalence of Rhesus (Rh) negativity and neonatal outcomes among pregnant women who
delivered at Bule Hora University Teaching Hospital over a 5-year period from January 2017 to December 31, 2022.
Methods: A retrospective study was conducted on 110 women who delivered at Bule Hora University Teaching Hospital (BHUTH) from
January 2017 to December 31, 2021. The complete data of the mother’s and neonates’ status were extracted from the registration book of
the hospital using checklists. The data were double entered using EpiData version 3 and exported to the Statistical Package for Social
Sciences (SPSS) version 26 for analysis. Descriptive statistics to determine prevalence and frequencies were used to describe the study
population in relation to relevant variables, and the results are presented in tables and charts.
Results: The study shows that the prevalence of Rh D-negative among women who delivered was 6.4% [95% CI: 1.83,10.98]. Among
Rh-negative women, 1 (25%) of blood group AB, 3 (6.5%) of blood group O, and 2 (6.1%) of blood group A were Rh-D negative. The distri�butions of O, A, B, and AB blood groups among pregnant women who delivered this hospital were 41.8%, 30%, 24.6%, and 3.6%, respec�tively. Out of neonates born to Rh-negative women, 1 (14.3%) was born with jaundice. Of women who delivered at BHUT hospital, 61
(55.5%) did not have a previous delivery, 7 (6.4%) had a previous abortion, 5 (4.5%) stillbirth, 1 (0.9) died after birth, 4 (3.6%) had a birth
child weight less than 2.6 kg.
Conclusion: The study revealed that the prevalence of Rh-negative was comparable with finding of different similar studies. To reduce
Rh incompatibility-related HDN, the government should educate mothers and encourage them as they follow ANC facilities and after deliv�ery to health facilities.
Medication abortion represents more than 50 percent of abortions in the United States (US). Since its approval in the US in 2000, the Food and Drug Administration (FDA) has progressively relaxed the prescribing requirements such that currently, no office visit, in-person dispensing, or ultrasound is required. Obtaining medication for abortion online without medical supervision or evaluation is also possible. This article reviews the complications of medication abortion by examining major studies and delineates the risks specific to self-managed abortion to inform clinicians in caring for women.
Summary: Medication abortion has become the most common abortion method in the United States. This document provides a detailed history of the relaxation requirements on medication abortion and reviews the major studies on medication abortion complications including a discussion of their limitations. Finally, the paper delineates the ease of access to medication abortion without a health care provider and the risks associated with self-managed abortion. This paper is intended to provide information for clinicians who likely will be encountering increasing number of patients with such complications.
Background
The RH system is one of the most polymorphic blood group systems due to the proximity and opposite orientation of RHD and RHCE genes. Numerous alleles are described and can affect Rh protein expression. This complexity is especially evident in populations of African origin. We performed RHD and RHCE genotyping of the Noir Marron population in French Guiana. This population belongs to the Maroon community who are direct descendants of African slaves, who escaped from Dutch plantations, in the current day Suriname, during the 17th century. They represent an original ethnic group with highly blended culture.
Methods and materials
A total of 89 DNA samples were collected from four different ethnic groups of the Noir Marron population of French Guiana. RHD and RHCE genotyping was performed using DNA microarray and/or sequencing.
Results and discussion
Significant allelic diversity was shown, with 45% of individuals presenting an RHD gene variant (most common: RHD*DAU, RHD*DIVa, and RHD*DIIIa allele) and 9.4% with a partial D phenotype. Likewise, 85% presenting an RHCE gene variant and 9% a partial RH2 antigen. One original allele was identified in two D+ Noir Marron individuals: a hybrid RHD*DIIIa‐CE(9)‐D allele, encoding probably a partial D antigen and associated with an RHCE*ce(48C,733G,1006T) allele.
The African diversity of RHD and RHCE genes is found in this population with preserved genetic but mixed cultural backgrounds. These data allow us to describe the characteristics of the RH system antigen and highlights a significant number of partial antigens with a risk of alloimmunization.
Introduction
Hemolytic disease of the fetus and newborn (HDFN) is a condition caused by maternal alloantibodies against fetal red blood cells (RBCs) that can cause severe morbidity and mortality in the fetus and newborn. Adequate screening programs allow for timely prevention and intervention resulting in significant reduction of the disease over the last decades. Nevertheless, HDFN still occurs and with current treatment having reached an optimum, focus shifts towards non-invasive therapy options.
Areas covered
This review focusses on the timely identification of high risk cases and antenatal management. Furthermore, we elaborate on future perspectives including improvement of screening, identification of high risk cases and promising treatment options.
Expert opinion
: In high-income countries mortality and morbidity rates due to HDFN have drastically been reduced over the last decades, yet worldwide anti-D mediated HDFN still accounts for 160.000 perinatal deaths and 100.000 patients with disabilities every year. Much of these deaths and disabilities could have been avoided with proper identification and prophylaxis. By implementing sustainable prevention, screening and disease treatment measures in all countries this will systemically reduce unnecessary perinatal deaths. There is a common responsibility to engage in this cause.
Maternal alloimmunization is still the leading cause of fetal anemia and is responsible for neonatal mortality and morbidity in developing countries. Evidence-based guidelines are essential for implementing antenatal alloantibodies screening in developing countries like India which will help to formulate recommendations and reduce adverse outcomes of Hemolytic disease of fetus and new born.
To determine the frequency of alloimmunization among in Antenatal women during routine antenatal visits irrespective of Rh status.
The prospective study carried out in a tertiary care hospital has enrolled 1000 antenatal women (500 each of Rh-positive and Rh-negative women) attending antenatal clinics and admitted for institutional deliveries, were screened for red cell alloimmunization and association between alloimmunization rate in antenatal women with variables was carried out to determine the clinical significance.
Among 1000 antenatal women enrolled and screened 33 (3.3%) antenatal women were found to be alloimmunized. The prevalence of alloimmunization among Rh-negative women is 5.4% (27/500). While the prevalence of alloimmunization among Rh-positive women is 1.2% (6/500). Majority of the alloimmunized cases were multigravida. 75.7% (25/33) antibodies identified in our study were anti-D antibodies and 24.24% (8/33) were non anti-D antibodies.
Successful implementation of Antenatal antibody screening program requires a coordinated Team approach between the Transfusion medicine, Obstetrics, Radiology and Pediatrics departments. Early screening irrespective of Rh status and effective utilization of RhIg prophylaxis in Rh negative antenatal women is the only solution to reduce fetal, neonatal morbidity and mortality due to alloimmunization.
This authoritative textbook provides a much-needed guide for postgraduate trainees preparing for the European Board and College of Obstetrics and Gynaecology (EBCOG) Fellowship examination. Published in association with EBCOG, it fully addresses the competencies defined by the EBCOG curriculum and builds the clinical practice related to these competencies upon the basic science foundations. Volume 1 covers the depth and breadth of obstetrics, and draws on the specialist knowledge of four highly experienced Editors and over 100 contributors from across Europe, reflecting the high-quality training needed to ensure the safety and quality of healthcare for women and their babies. It incorporates key international guidelines throughout, along with colour diagrams and photographs for easy understanding. This is an invaluable resource, not only for postgraduate trainees planning to sit the EFOG examination, but also for practising specialists looking to update their knowledge and skills to meet the ever-evolving complexity of clinical practice.
With advances in ultrasound, birth defects are increasingly detected during pregnancy and may be amenable to surgical correction before delivery, to improve outcomes. This essential book discusses the different birth defects that can be treated during pregnancy and the important anesthetic considerations for the mother and fetus undergoing these procedures. Experts in the fields of anesthesiology, maternal fetal medicine, surgery, and pediatrics have come together to develop the content of this book. Enhanced throughout with full color images and illustrations, the book covers important topics such as spina bifida, twin-twin transfusion syndrome, sacrococcygeal teratoma, and lung masses, as well as fetal cardiac intervention, intrauterine transfusion, ex utero intrapartum treatment, and multidisciplinary approaches to fetal surgery. An invaluable guide for pediatric and obstetric anesthesiologists, anesthesiology, obstetrics, and surgical trainees, nurse anesthetists, and maternal-fetal medicine specialists.
Introduction:
Despite the availability guidelines to prevent RhD alloimmunization, severe hemolytic disease of fetus and newborn still occurs in high-income countries. The aim of the study was (1) To assess variations in practices for the prevention of RhD alloimmunization, and (2) to understand midwives' acceptance and appropriation of fetal RhD genotyping.
Methods:
Descriptive cross-sectional survey of French midwives from September 2017 through January 2018. Participants were asked to complete an internet-based questionnaire that included three clinical vignettes. They were questioned about their practices concerning early pregnancy visit by RhD-negative women, prevention of RhD alloimmunization in women with second-trimester metrorrhagia, and RhD fetal genotyping.
Results:
A total of 827 midwives completed the questionnaire. Only 21.1% reported that they practice all the preventive measures recommended in early pregnancy. In a situation at high risk of RhD alloimmunization during pregnancy, 97.2% of midwives would perform immunoprophylaxis. Nearly, all midwives reported providing information about RhD alloimmunization (92.4%) at the beginning of pregnancy, although only 11.3% offered both written and verbal information; at the time of systematic anti-D immunoprophylaxis (28 weeks), 78% provided information, but only 2.7% both verbally and in writing. Finally, only 50.8% of midwives preferred to include RhD fetal genotyping in routine prenatal prophylaxis.
Discussion:
This study showed significant variations in French midwives' practices to prevent RhD alloimmunization. Better dissemination of guidelines is needed to improve both consistent use of these practices and the quality of information delivered to RhD-negative pregnant women.
This article attempts to highlight contemporary issues relating to term neonatal hyperbilirubinemia and to focus attention on controversial issues and concepts with the potential to effect change in clinical approach. On the one hand, the focus is bilirubin neurotoxicity, which is now known to encompass a wide, diverse spectrum of features. The various aspects of this spectrum are outlined and defined. On the other hand, bilirubin also possesses antioxidant properties. As such, mild hyperbilirubinemia is suggested as actually offering the neonate some protective advantage.
AimTo determine the socio-demographic characteristics and pregnancy outcome of Rh D alloimmunized women monitored with MCA PSV (middle cerebral artery peak systolic velocity).Materials and Methods
In total, 363 Rh D alloimmunized women attended antenatal clinic or obstetric emergency between January 2006 and December 2014. MCA PSV was the screening method for detection of fetal anemia. Intrauterine blood transfusion (IUT) was given when MCA PSV was > 1.5 MOM. Totally, 162 women (164 fetuses) received 492 transfusions. Forty-eight women had fetal hydrops at presentation. Five women (three received IUT) were lost to follow-up. Pregnancy outcome of 358 women and socio-demographic characteristics of 363 women were analyzed.ResultsThe perinatal mortality was 421, 66 and 87 per 1000 live births in hydrops group, non-hydrops IUT group and non-IUT group, respectively.Conclusion
Rh alloimmunization is still a major cause of perinatal morbidity and mortality. The higher gravidity, previous history of pregnancy wastage, still births and hydrops increase the requirement of intrauterine transfusion. MCA PSV is an excellent tool for monitoring of Rh alloimmunized pregnancies to detect fetal anemia. Early detection and monitoring by MCA PSV improve its outcome.
Neonatal hematology is a fast-growing field, and the majority of sick neonates will develop hematological problems. This is an essential guide to the pathogenesis, diagnosis and management of hematologic problems in the neonate. Guidance is practical, including blood test interpretation, advice on transfusions and reference ranges for hematological values. Chapters have been thoroughly revised according to the latest advances in the field for this updated third edition. Topics discussed include erythrocyte disorders, platelet disorders, leukocyte disorders, immunologic disorders and hemostatic disorders. Coverage of oncological issues has been expanded to two separate chapters on leukemia and solid tumors, making information more easily accessible. Approaches to identifying the cause of anemia in a neonate are explained, with detailed algorithms provided to aid clinicians in practice. Covering an important hematologic niche with an ever increasing amount of specialized knowledge, this book is a valuable resource for hematologists, neonatologists and pediatricians.
The predominant cause of elevated total/plasma bilirubin (TB) levels is from an increase in bilirubin production primarily because of ongoing hemolysis. If undiagnosed or untreated, the risk for developing extreme neonatal hyperbilirubinemia and possibly bilirubin-induced neurological dysfunction (BIND) is increased. Since carbon monoxide (CO) and bilirubin are produced in equimolar amounts during the heme catabolic process, measurements of end-tidal CO levels, corrected for ambient CO (ETCOc) can be used as a direct indicator of ongoing hemolysis. A newly developed point-of-care ETCOc device has been shown to be a useful for identifying hemolysis-associated hyperbilirubinemia in newborns. This review summarizes the biology of bilirubin production, the clinical utility of a novel device to identify neonates undergoing hemolysis, and a brief introduction on the use of ETCOc measurements in a cohort of neonates in China.
ABO and Rhesus (Rh) blood group antigens are hereditary characters and are useful in population genetic studies, in resolving medico-legal issues and more importantly in compatibility test in blood transfusion practice. Data on frequency distribution of ABO and Rh-D in Niger-Delta region of Nigeria are not available; hence we made an attempt to retrospectively analyze the records on the blood donors, transfusion recipients and patients attending antenatal care or some other medical interventions. Over a twenty-year period between 1986 and 2005, a total of 160,431 blood samples were grouped for ABO and Rh-D at the blood bank of the University of Benin Teaching Hospital, Benin City, Nigeria. Blood group distribution among these samples showed phenotypes A, B, AB and O as 23.72%, 20.09%, 2.97% and 53.22%, respectively. The Rh-D negative phenotype was found among 6.01% of the samples tested.
To determine the prevalence of different blood groups and Rh factors in a random population sample from urban and rural areas of Rawalpindi and Islamabad region of Pakistan.
Blood group and Rh factor determination was carried out by the antigen-antibody agglutination test from October 2003 to October 2004, and encompassed 2518 subjects.
The percentages of various groups among male and female subjects, respectively, were recorded as 27.01% and 24.02% (for blood group A), 33.75% and 32.87% (for blood group B), 8.93% and 11.20% (for blood group AB) and 30.31% and 31.91% (for blood group O). The Rh positive and negative distribution in the studied population was 92.45% and 7.55% respectively.
The determination of the frequency of blood groups in the region would not only help in blood transfusion services, but also eliminate the risk of erythroblastosis foetalis in the neonates.
An anti-Rh gamma2-globulin antibody preparation has been developed which can be administered intramuscularly and appears to be both safe and effective in the prevention of experimental Rh sensitization. Nine unsensitized Rh-negative male volunteers were challenged once a month for five successive months with intravenous injections of 2 ml. of Rh-positive blood. Four of these nine volunteers were passively protected each month with intramuscular injections of 5 ml. of this antibody preparation, administered 24 hours prior to the antigenic challenge. Three months after the last injection the passively acquired Rh antibodies were no longer demonstrable (by either the saline or indirect antiglobulin technics) in any of the four protected subjects and there was no sign of active antibody production six months after the last injection, whereas four of the five controls were all strongly sensitized.
The number of Rh-isoimmunized pregnancies in Manitoba has been reduced from 223 and 228 in the years ending Oct. 31, 1963 and 1964 to 60 and 62 in the years ending Oct. 31, 1974 and 1975. The number per 1000 total births in the same years has decreased from 10.0 and 10.6 to 3.4 and 3.5 Perinatal mortality rates in those years decreased from 13.8 amd 15.7% to 0 and 2.2%, respectively. The number of perinatal deaths has been reduced from 55 in the first 2 years reported to 1 in the last 2 years. Among the 121 isoimmunized women pregnant in the 2-year period ending Oct. 31, 1975, isoimmunization was due to failure to give Rh immune globulin after delivery in 33 and failure to give it during pregnancy in 48. Of the remaining 40, 37 were immunized before Rh immune globulin became available. Complete prevention of Rh isoimmunization and therefore of all perinatal deaths from Rh erythroblastosis can only be achieved through universal Rh testing prenatally and immediately after delivery, and institution of an antenatal Rh prophylaxis program.
The retrospective study was carried out in 38,898 healthy adult blood donors of both sexes, recruited mainly from Nairobi area in Kenya. The percentage proportions of blood groups were: group 0-47.4, group A-26.2, group B-22.0 and group AB-4.4. In all the samples, there were 96.1% Rh (D) positive blood donors. Among these were 0.75% subjects with Rh (D) variant antigen Du positive. Rh (D) negative was only 3.9% among the blood donors. There is a real preponderance of the blood group 0 over the blood groups A, B and especially AB as well as Rh (D) positive over Rh (D) negative. The authors found following frequencies of genes: p(A)0.168, q(B)0.142, r(0)0.690, D positive 0.804, D negative 0.196 and compare their own results with the data of other investigators concerning other Kenyan and African populations.
The question whether India should institute a national programme of Rh screening and postpartum Rh immune globulin prophylaxis needs to be addressed, especially because of the recent emphasis on primary maternal and child health care. Given the absence of relevant community based data, decision analysis techniques were used to address these issues. The results reveal that the estimated cost per case of Rh HDN prevented through postpartum immune globulin prophylaxis is lower than the cost per case of Rh HDN treated through a curative strategy. However, the financial and infrastructural requirements of the preventive programme mean that such prevention may not be feasible at present. With the achievement of the Indian Government's stated objectives of population control, however, disease incidence should fall by 30% from 5.90/1000 births in 1981 to 4.13/1000 births by the year 2000, even in the absence of a prophylaxis programme.
A retrospective review of obstetric records for 1979 in two major Calgary hospitals was undertaken to determine the rate of compliance with postpartum Rh isoimmunization prophylaxis in Alberta. The charts of 4528 women ranging in age from 13 to 46 years were reviewed. The prevalence rate of Rh negativity was found to be 16%. Of the 710 Rh-negative women 490 (69%) were eligible to receive Rh immune globulin (RhIG); that is, they had no anti-D antibodies, and the baby/fetus was Rh-positive or Rh-unknown. RhIG had been administered to 93.6% of the eligible women; the compliance rate ranged from 66.7% for obstetric emergencies (i.e., spontaneous abortion, antepartum or early-pregnancy hemorrhage, or ectopic pregnancy) to 98.2% for postpartum diagnoses. In more than half (54.7%) of the women who underwent amniocentesis Rh type was not determined; the implications of this finding are discussed. Although poor compliance with postpartum RhIG administration is not a reason for withholding antepartum administration of RhIG, maximum compliance with the more cost-effective programs should be attained before antepartum programs are fully implemented.
For two decades the perinatal mortality caused by erythroblastosis has been decreasing in Manitoba. The improved management of Rh-immunized pregnancies has lowered the death rate among affected infants from 10.8% to 3.4%, while the prevention of Rh immunization has reduced its incidence from 9.1 to 2.2 per 1000 total births. In its first 6 years and 8 months Manitoba's antenatal prophylaxis program, in which immunoglobulin is administered to Rh-negative women at 28 weeks' gestation, reduced the incidence of Rh immunization during pregnancy by 93%. In combination with post-abortion and postpartum prophylaxis the antenatal treatment has provided a protection rate of 98.6% among primigravidas at risk. Further improvements are expected.
The ABO and Rhesus blood group systems remain the most important blood group systems clinically. In order to provide gene frequency values for the ABO and Rh (D) alleles in a healthy infant population in south west Nigeria, 4748 healthy infants were typed for ABO and Rh (D) blood groups over a five year period (1988-1992). Overall, 2575 (54.2%) were blood group O, 1023 (21.6%) were blood group A, 1017 (21.4%) were blood group B and 133 (2.8%) were blood group AB. The distribution of the ABO blood groups did not differ significantly from those expected under the Hardy Weinberg equilibrium (Goodness-of-fit X2 = 6.09, df = 3, p = 0.1075). The proportions of the infants belonging to the various ABO blood groups did not vary significantly over the period of the study (X2 = 14.53, df = 12, p = 0.268). Overall gene frequencies for the O, A and B genes were 0.7398, 0.1305 and 0.1298 respectively. For the Rh (D) gene, 4520 (95.2%) were Rh-positive while 228 (4.8%) were Rh-negative. However, the proportions of Rh (D) negative infants varied significantly over the period of the study, with a particular year (1991) having nearly twice the usual frequency of Rh-negative individuals (X2 = 31.17, df =, p < 0.001). The frequency of the Rh (D) gene was 0.7809. These figures are reported in the hope that they may find some use as reference for studies of ABO blood groups in health and disease, especially since they were obtained in an infant population in which it is expected that selection pressures should not have started to act to any significant extent.
To determine the incidence of clinically significant allo-antibodies in antenatal care (ANC) patients, and make recommendations on laboratory management of such cases in similar settings in Zimbabwe.
A retrospective study.
Harare Central Hospital, a tertiary medical centre in Harare.
Patients attending the ANC clinic at Harare Central Hospital.
Blood group tests, allo-antibody screen, development of haemolytic disease of the newborn.
3,000 patients were grouped and screened and 96.7% were found to be Rhesus positive, 0.5% were Rhesus Du positive and 2.8% were Rhesus negative. An overall antibody incidence of 1.7% (n = 50) was obtained, 1.0% (n = 30) of which were strongly positive and 0.7% (n = 20) were so weakly positive so that no antibodies could be identified. Antibodies identified from those patients with strongly positive antibody screen were anti-D 13.3% (n = 4), anti-E 6.7% (n = 2), anti-Jsb 3.2% (n = 1), anti-Lea 23.3% (n = 7) and anti-Leb 20% (n = 6). Antibodies of unknown specificity were detected from 20% (n = 6) of the patients. Four (13.3%) of the specimens were insufficient for antibody identification. Clinical records of those patients with a strongly positive antibody screen were examined and anti-D and anti-Jsb were observed to have caused severe to fatal Haemolytic Disease of the Newborn (HDN). The four anti-D positive cases resulted in two still births and two jaundiced babies. The single anti-Jsb positive antibody case resulted in an intra-uterine death. Antibodies that are generally considered of no clinical significance did not cause HDN in this study.
Anti-D remains the most important allo-antibody causing HDN, regardless of the availability of anti-D immunoglobulin for prophylaxis. Only Rhesus D negative women and those who have clinically significant antibodies need have repeat antibody screens during the rest of the pregnancy. In line with the current policy of screening all patients at booking, the policy on repeats is not clear and was not evident in this study.
Alloimmunisation to Rhesus D (RhD) is a major factor in perinatal morbidity and may result in the compromise of the woman's obstetric career. In Nigeria accurate population based studies to determine the prevalence of Rhesus negative women and the incidence of alloimmunisation are lacking, hence we undertook to study pregnancy outcome in Rhesus negative women.
We studied retrospectively sixty-seven RhD negative women over a two year period; information was obtained from the case-file of all pregnant women who presented to the ante-natal clinic and were identified as Rhesus negative. This was corroborated with the blood bank record over the same period.
Forty per cent of these were nulliparae with an average of 0.5 abortions. Only 20% had the blood groups of their husbands documented, and only four babies born to these women had their Rhesus group recorded. Six of the babies appeared to have been severely affected by Rhesus isoimmunisation. Three of these had an exchange blood transfusion (EBT); all who had an EBT had a satisfactory outcome. Out of the other three, there were two neonatal deaths and one fresh stillbirth. Fourteen babies had neonatal jaundice with a mean bilirubin level of 6 mg/dl, all of which were mainly unconjugated. Evidence for the administration of anti D was obtained in only three patients; all had one ampoule (dose in i.u and/or _g not stated) administered within 72 hr.
This preliminary study has shown that isoimmunisation due to Rhesus incompatibility is poorly studied among Nigerian women with many questions unanswered; therefore there is an urgent need for a management protocol for this condition, which will include both the clinicians and the laboratory physicians.
To assess the prevalence of Rh-negative pregnant women who attended the antenatal clinic and delivered in Rajavithi Hospital.
A descriptive retrospective study in Rh-negative pregnant women was done. The present study included the general characteristic of cases, anti-D immunoglobulin prophylaxis administration, fetal anemia and neonatal jaundice.
During the study period, 147 Rh-negative pregnant women delivered at Rajavithi Hospital. The prevalence of Rh-negative pregnant women in Rajavithi hospital was 0.31%. Fetal anemia and neonatal jaundice were detected in 21.9% and 37.2%, respectively, and 68.14% of cases received antenatal anti-D immunoglobulin. Anti-D immunoglobulin prophylaxis significantly reduced the incidence of neonatal jaundice (p < 0.05).
The prevalence of Rh-negative pregnant women was 0.31%.