Materiały źródłowe

• #1 Rh Incompatibility: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/797150-overview

  Only 15% of the population lack the Rh erythrocyte surface antigen and are considered Rh-negative. The vast majority (85%) of individuals are considered Rh positive. Rh sensitization occurs in approximately 1 per 1000 births to women who are Rh negative. The Southwest United States has an incidence approximately 1.5 times the national average, which likely is caused by immigration factors and limited access to medical care, since blood typing is a routine part of prenatal care. Even so, only 17% of pregnant women with Rh-negative blood who are exposed to Rh-positive fetal blood cells ever develop Rh antibodies. […] Approximately 15-20% of White patients, as opposed to 5-10% of Black patients, have the Rh-negative blood type. Among individuals of Asian and American Indian descent, the incidence of Rh-negative blood type is less than 5%.

• #1 Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels | Pediatric Research

  https://www.nature.com/articles/pr2013208

  Inconsistent use of definitions and management approaches limit the use of available data at both national and global levels. […] We report systematic estimates for the prevalence, mortality, and neurodevelopmental outcomes of Rh disease and EHB due to other causes, e.g., G6PD deficiency, prematurity, neonatal hemolysis, and idiopathic causes. […] Countries with a neonatal mortality rate (NMR) 5 were therefore presumed to have good Rh prophylaxis and strong health systems, with very few cases of Rh disease. […] In 2010, an estimated 373,300 babies were affected with Rh hemolytic disease worldwide. […] The global estimated prevalence for Rh disease was 276/100,000 live births. […] Our estimates suggest that Rh disease accounts for the majority of the total global EHB burden (uncertainty range: 271,800477,500). […] The failure to prevent Rh sensitization and manage EHB results in the global burden of neonatal hyperbilirubinemia falling most heavily on the worlds poorest countries, especially in South Asia and sub-Saharan Africa.

• #1 Erythroblastosis Fetalis: Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/erythroblastosis-fetalis

  Approximately 276 per 100,000 live births worldwide involve pregnancy complications related to Rh-blood type incompatibility. Researchers estimate that without treatment, there’s about a 50% chance that the fetus will die or experience severe health issues. […] In parts of the world with easy access to prenatal care, only 2.5 per 100,000 births involve problems related to Rh-blood type incompatibility. […] As part of routine prenatal care in the United States, you’re screened for blood type and the presence of any antibodies. If you’re pregnant and have Rh-negative blood, your provider will screen for antibodies to Rh-positive blood. […] If you test positive for the antibodies, this means there’s a risk your immune system will attack the fetus’s red blood cells if they’re Rh-positive. […] Erythroblastosis fetalis is highly preventable with prenatal care that includes blood type testing and preventive medication. If you’re Rh-negative, taking Rh immune globulin (RhIg or RhoGAM) can prevent your body from making antibodies against Rh-positive blood.

• #1 Hemolytic disease of the fetus and newborn and Rhesus alloimmunization in Latin American countries: a scoping review | BMC Pregnancy and Childbirth | Full Text

  https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-024-07044-3

  The estimated worldwide prevalence of severe Rh disease in 2010 was 277/100,000 live births, contrasting with estimates of 2.5/100,000 live births in high-income countries with established perinatal/neonatal care. Furthermore, the same study estimated a higher prevalence of Rh disease in low-to-middle income countries, namely, 525 in Eastern Europe/Central Asia, 386 in sub-Saharan Africa, and 345 in Latin America/Caribbean countries, per 100,000 live births. […] The available data may be underestimated due to diagnostic failure, underreporting of cases, and the lack of a systematic investigation and monitoring policy for these conditions. […] Overall, the frequency of Rh alloimmunization ranged between 1.5% and 3.8% of pregnancies. […] The presence of hydrops significantly increases fetal mortality (30% vs 8%, RR: 3.5 [95% CI 1.6 to 7.9]). […] The incidence, morbidity, and mortality of HDFN in the LATAM region are troublesome, and RhD alloimmunization is reported in up to approximately 70% of severe HDFN cases.

• #1 Haemolytic Disease of the Fetus and Newborn (HDFN)

  https://patient.info/doctor/haemolytic-disease-of-the-fetus-and-newborn

  The incidence of haemolytic disease of the newborn (HDN) depends on the proportion of the population who are RhD negative; 15% of White populations (North Americans and Europeans) are found to be Rh-negative, while only 4%-8% of African and 0.1%-0.3% of Asian populations have the Rhesus negative blood group. Before immunoprophylaxis was available, HDN affected 1% of all newborns and was responsible for the death of one baby in every 2,200 births. […] Anti-D prophylaxis (mostly administered postnatally) and advances in neonatal care have reduced the frequency of HDN by almost a factor of 10 to 1 in 21,000 births. Deaths attributed to RhD alloimmunisation fell from 46/100,000 births before 1969, to 1.6/100,000 in 1990. This may not be entirely attributable to immunoglobulin; changes in abortion rates and racial composition may also play a part. One American study quoted a prevalence of RhD alloimmunisation of 6 in 1,000 births and suggests that this should now be considered a rare condition.

• #1 Rh hemolytic disease. Epidemiologic surveillance in the United States, 1968 to 1975 – PubMed

  https://pubmed.ncbi.nlm.nih.gov/113567/

  Nationwide surveillance of Rh hemolytic disease of the newborn showed that associated infant mortality decreased from 941 deaths in 1968 to 269 deaths in 1975, or from 2.7 to 0.9 per 10,000 live births. The incidence of Rh hemolytic disease declined from 45 per 10,000 total births in 1970 to 21 per 10,000 in 1975. […] Several state-based Rh disease surveillance programs reported declining mortality and incidence and increasing use of Rh immune globulin. Rh immune globulin was administered to an estimated 80% of eligible Rh-negative women in 1974, eighty-one percent in 1975, and 82% in 1976. More concerted efforts are needed to determine the frequency of maternal sensitization and to identify and correct gaps in postpartum and postabortion use of Rh immune globulin.

• #1 Hemolytic Disease of the Newborn: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/974349-overview

  Hemolytic disease of the fetus and newborn (HDFN) affects an estimated 3-80 in 100,000 patients annually. […] Before the establishment of modern therapy, 1% of all pregnant women developed Rh alloimmunization. Since the advent of routine prophylaxis of at-risk women, incidence of Rh sensitization has declined from 45 to 10.2 cases per 10,000 births, with less than 10% requiring intrauterine transfusion. […] Alloimmunization due to Kell antigen accounts for 10% of severely affected fetuses. […] Currently, anti-D is still one of the most common antibodies found in pregnant women, followed by anti-K, anti-c, and anti-E. Of those fetuses who require intrauterine transfusions, 85%, 10%, and 3.5% were due to anti-D, anti-K, and anti-c, respectively. […] ABO incompatibility frequently occurs during the first pregnancy and is present in approximately 12% of pregnancies, with evidence of fetal sensitization in 3% of live births. Less than 1% of births are associated with significant hemolysis.

• #1 Hemolytic Disease of the Newborn: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/974349-overview

  Incompatibility involving Rh antigens (anti-D or anti-c) occurs in about 10% of all pregnancies among Whites and Blacks; in contrast, it is very rare in Asian women. […] Fetal sex plays a significant role in the degree of response to maternal antibodies. An apparent 13-fold increase is observed in fetal hydrops in RhD-positive male fetuses compared with female fetuses in similarly sensitized pregnancies.

• #1 Hemolytic disease of the fetus and newborn due to Rh(D) incompatibility: A preventable disease that still produces significant morbidity and mortality in children | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235807

  In the mid-20th century, Hemolytic Disease of the Fetus and Newborn, caused by maternal alloimmunization to the Rh(D) blood group antigen expressed by fetal red blood cells (i.e., Rh disease), was a major cause of fetal and neonatal morbidity and mortality. […] To investigate global compliance with this therapeutic intervention, we used an epidemiological approach to estimate the current annual number of pregnancies worldwide involving an Rh(D)-negative mother and an Rh(D)-positive fetus. […] Our results suggest that ~50% of the women around the world who require this type of immunoprophylaxis do not receive it, presumably due to a lack of awareness, availability, and/or affordability, thereby putting hundreds of thousands of fetuses and neonates at risk for Rh disease each year. […] However, a review of the literature revealed very few publications describing the prevalence of Rh(D) disease in low income countries, where it is not generally considered to be a major problem, presumably due to a lower prevalence of the Rh(D)-negative blood type than in high income countries and an absence of data collection and disease monitoring for this disorder.

• #1 Rhesus immunisation in Australia | NHMRCNHMRCNHMRC TaglineNHMRC Tagline

  https://www.nhmrc.gov.au/about-us/resources/impact-case-studies/rhesus-immunisation-australia

  Haemolytic disease of the fetus and newborn (HDFN, also known as Rh Disease) can occur during pregnancy when a pregnant woman’s immune system produces antibodies that attack their fetus’ red blood cells (RBCs). […] Today, HDFN is almost non-existent in Australia due to routine antenatal blood grouping and antibody screening, and the use of prophylactic Rh D immunoglobulin and appropriate clinical management of mother and baby. […] Without intervention, HDFN affects 1% of babies and is a significant cause of perinatal mortality and morbidity. Today, HDFN is largely preventable due to the development of Rh D immunoglobulin. […] Clinical incidence of HDFN is almost non-existent in Australia due to the discovery of Rh D immunoglobulin in conjunction with routine antenatal screening for Rh blood groups and appropriate management of mother and baby.

• #1 Grand Rounds: Rh disease: It’s still a threat

  https://www.contemporaryobgyn.net/view/grand-rounds-rh-disease-its-still-threat

  Once a common cause of perinatal death, Rh disease is now quite rare in pregnant women, thanks in large part to advances in U/S and DNA technology. But the fact that roughly 7 out of every 1,000 liveborn infants are delivered by Rh-sensitized women emphasizes the need for more vigorous preventive efforts and up-to-date management skills. […] Despite these efforts, a recent review of the 2001 birth certificates in the US by the Centers for Disease Control and Prevention indicates that Rh sensitization still affects 6.7 out of every 1,000 live births. […] We are failing to prevent all cases of Rh alloimmunization for several reasons: inadvertent antenatal and postpartum omission, failure to use the drug for other antenatal indications, and insufficient dosing at delivery in the case of a large fetomaternal hemorrhage.

• #1 Guidelines for Rhesus Disease Prevention | Article | GLOWM

  https://www.glowm.com/article/heading/vol-16–the-prevention-and-management-of-rh-disease–guidelines-for-rhesus-disease-prevention/id/418863

  Introduction of anti-Rh(D) immunoglobulin more than 50 years ago, has only resulted in a 50% decrease of Rhesus (Rh) Disease globally, due to a low uptake of this prophylaxis. […] However, recent data have shown that, in approximately 50% of eligible cases worldwide, on an annual basis, no anti-Rh(D) immunoglobulin is administered. […] It has been estimated that Rh Disease still results in more than 160,000 perinatal deaths and 100,000 cases of disability annually; only a 50% reduction as compared to the era before immunoglobulin administration. […] In 2021 the Federation of Gynecology and Obstetrics (FIGO) has published guidelines on the prevention of Rh Disease by immunoprophylaxis, considering the cost effectiveness of the different dose regimens and prioritizing its administration by indication.

• #1 Globally, Only Half of Women Get Treatment for Rh Disease | Columbia University Irving Medical Center

  https://www.cuimc.columbia.edu/news/globally-only-half-women-get-treatment-preventable-killer-newborns

  This treatment is the standard of care for preventing Rh disease, but we recognize that there remain significant obstacles to expanding access to this lifesaving therapy around the world. […] The burden of Rh disease in lower-income countries is not well known; the most recent estimates are based on reported rates of neonatal complications associated with Rh incompatibility. […] The study found an annual worldwide gap of more than 2.5 million doses below the minimum recommended threshold for preventing Rh disease. […] In particular, in 100 countries, fewer than 80% of pregnant women who required the therapy received a dose after delivery. […] The biggest shortfalls occur in South Asia and Sub-Saharan Africa: Both regions have a high incidence of neonatal deaths due to complications of Rh disease, but virtually no Rh(D) immunoglobulin was dispensed.

• #1 LSHTM LSHTM Research Online

  https://researchonline.lshtm.ac.uk/1440281/

  BACKGROUND: Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden. […] Twenty-four million (18% of 134 million live births 32 wk gestational age from 184 countries; uncertainty range: 23-26 million) were at risk for neonatal hyperbilirubinemia-related adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800-477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000-131,000), with a 24% risk for death (114,100; uncertainty range: 59,700-172,000), 13% for kernicterus (75,400), and 11% for stillbirths. […] Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. […] Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries.

• #1 Prevention of Rhesus (Rh) disease of newborns in Pakistan | The Morris Lab | SickKids | The Morris Lab

  https://lab.research.sickkids.ca/morris/ongoing-research/prevention-of-rhesus-rh-disease-of-newborns-in-pakistan/

  Rhesus (Rh) hemolytic disease is a preventable disease of the newborn that is caused by an incompatibility between maternal and fetal red blood cells. […] Despite the availability of effective screening and prevention strategies that have contributed to the near eradication of Rh disease in high-income countries, the burden of Rh disease remains disproportionately high in low- and middle-income countries (LMICs). […] Globally, 373,300 live births, or 276 babies per 100,000 live births, were estimated to be affected by Rh disease in 2010. […] The prevalence of the disease is estimated to be greatest in countries with neonatal mortality rates equal to or greater than 15 newborn deaths per 1000 live births. […] The first step towards preventing Rh disease of the newborn is the early identification and prophylactic treatment of Rh(D)-negative women with two doses of anti-D immunoprophylaxis (RhIg).

• #1 Hemolytic disease of the fetus and newborn due to Rh(D) incompatibility: A preventable disease that still produces significant morbidity and mortality in children | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235807

  Therefore, the main objective of the present study is to attempt to quantify the worldwide gap between the annual number of doses of IgG anti-Rh(D) that should theoretically be administered to minimize the risk of Rh(D) sensitization, and the annual number of doses of IgG anti-Rh(D) that are actually administered. […] The annual number of doses of IgG anti-Rh(D) required to provide antenatal and post-partum immunoprophylaxis by GBD Super Region is shown in Table 1, together with the total number of annual doses actually administered and the difference between the number of IgG anti-Rh(D) doses required for post-partum immunoprophylaxis and the number actually administered. […] However, fewer than 4 million doses are currently administered annually; this outcome does not even achieve the minimum threshold for preventing Rh(D) sensitization by providing only post-partum immunoprophylaxis, which would require more than 5 million doses annually.

• #1 Globally, Only Half of Women Get Treatment for Rh Disease | Columbia University Irving Medical Center

  https://www.cuimc.columbia.edu/news/globally-only-half-women-get-treatment-preventable-killer-newborns

  The researchers found that none of the regions studied had acceptable levels of adherence to recommended guidelines for preventing Rh disease. […] A variety of factors, including lack of awareness of Rh incompatibility, limited availability of the therapy, and other health care priorities, play a role in hindering access to this life-saving therapy around the world. […] Now that we have a better understanding of these gaps in treatment, we can begin to address them on a regional level.

• #1

  https://step1.medbullets.com/hematology/111089/rh-hemolytic-disease-of-the-newborn

  Rh hemolytic disease of the newborn is caused by Rh incompatibility […] 15% of the population is Rh-negative […] history of prior blood transfusion […] previous pregnancy […] mother is Rh-negative, and father is Rh-positive or unknown […] prior administration of Rh IgG (RhoGam) […] history of invasive obstetric procedures.

• #1 Treatments for Fetal Rh Anemia – Medical Journalism Club

  https://voices.uchicago.edu/medicaljournalism/2022/05/27/treatments-for-fetal-rh-anemia/

  A recent 2016 study showed 0.3-0.6% of pregnancies are affected by HDFN (Dubey et al., 2019). About 15% of North Americans and Europeans are Rh negative, compared to 4-8% of Rh negative Africans and 0.1-0.3% of Rh negative Asians (Sarwar et al., 2021). In the US, the frequency of HDFN is more common due to the diversity and the amount of immigration that occurs. […] A study was done in 2013 to analyze the sensitization of females to determine the timing of RhD immunization during pregnancy and to determine when to administer anti-D prophylaxis. In 51% of the 290 Rhd immunized women experienced sensitization (were exposed to their babys Rh positive blood) during the first pregnancy, while 33% of the women experienced sensitization during the second pregnancy. In 94% percent of the pregnancies, Rh antibodies were developed after the first trimester. 73% of the women developed antibodies in the second or third trimester, while 21% developed them during or after delivery. The data collected gives reason for doctors to administer anti-D prophylaxis in the beginning of the third trimester (28-30 weeks) to all Rhd positive women carrying RhD negative fetuses (Tilbad et al., 2013).

• #1 Prevention of Rhesus Alloimmunization | Article | GLOWM

  https://www.glowm.com/article/heading/vol-3–elements-of-professional-care-and-support-before-during-and-after-pregnancy–prevention-of-rhesus-alloimmunization/id/412153

  The investigation of indirect maternal Coombs test is the first step to identify pregnant women susceptible to alloimmunization and those already alloimmunized. All pregnant women (D-negative or D-positive) should be screened at the first appointment for antibodies with the indirect anti-globulin test (indirect Coombs’ test). […] Immunoglobulin administration is indicated in the postpartum period of Rh-negative, non-sensitized women (negative indirect Coombs test) whose neonate is Rh-positive. […] If the RhD-negative pregnant woman does not receive anti-D IgG prophylaxis after the birth of a RhD-positive infant, the incidence of sensitization during pregnancy will be 12-16%. The rate of sensitization when prevention after birth is performed is 1.6-1.9%, while antenatal prophylaxis reduces the rate of sensitization during pregnancy to 0.2%.

• #1 Rhesus immunisation in Australia | NHMRCNHMRCNHMRC TaglineNHMRC Tagline

  https://www.nhmrc.gov.au/about-us/resources/impact-case-studies/rhesus-immunisation-australia

  Today, approximately 17% of women in Australia who become pregnant require Rh D immunoglobulin injections to prevent Rh disease and ensure their baby’s health. […] Lifeblood has maintained the Rh program collecting plasma from donors with anti-D for more than 50 years. There continue to be significant challenges in maintaining the supply of Rh D immunoglobulin in Australia due to the retirement of ageing donors, fewer new donors (due to fewer women developing anti-D antibodies following pregnancy or transfusion) and ethical concerns about increasing the anti-D levels in current donors. […] Following a systematic review of evidence and consensus by a multidisciplinary committee, NIPT for fetal RHD blood group genotype for all Rh D negative pregnancies in Australia was recommended in the Guideline for the prophylactic use of Rh D immunoglobulin in pregnancy care.

• #1 Guidelines for Rhesus Disease Prevention | Article | GLOWM

  https://www.glowm.com/article/heading/vol-16–the-prevention-and-management-of-rh-disease–guidelines-for-rhesus-disease-prevention/id/418863

  These measures are summarized in Table 1 and prioritized considering the cost effectiveness of the different dose regimens and prioritizing its administration by indication. When studying the gap between the annual doses of anti-Rh(D) given and the annual doses required, it can be concluded that the first priority is only met in high-income countries and in Brazil, Czech Republic, Croatia, Greece, Hungary, Iran, Lithuania, Malaysia, Saudi Arabia, Sri Lanka, South Korea, Thailand, Turkey, and Uruguay.

• #1 Immunohematological Surveillance of Rhesus D Negative Pregnancies in Under Equipped Area. About 34 Cases at Jason Sendwe General Hospital (Lubumbashi, Democratic Republic of Congo)

  https://www.gavinpublishers.com/article/view/immunohematological-surveillance-of-rhesus-d-negative-pregnancies-in-under-equipped-area-about-34-cases-at-jason-sendwe-general-hospital-lubumbashi-democratic-republic-of-congo

  Currently the antenatal diagnosis is the most recommended because it allows a management centered on actually risky pregnancies. […] Data on hemolytic fetal and rhesus-type neonatal disease in Africa indicate a lower frequency of negative rhesus D in the black population 15%/4%. […] Published studies of immunohematological surveillance of Rh D negative pregnancies indicate a lack of knowledge of Rh D negative status amongst healthcare workers and patients alike. […] The absence in our country of a protocol for immunohematological surveillance of negative Rh D pregnancies for the prevention of hemolytic disease in the newborn. […] The clinical profile of our allo immunizations revealed an allo immunizations of 76.47% of gestants in all groups and in Rhesus of 20%; the anti-D was accompanied by another antibody in 100% of cases and hemolytic disease of the newborn occurred in 62% of cases. […] Immunohematological monitoring of negative Rh D pregnancies in an under-equipped environment is feasible with the establishment of a multidisciplinary team.

• #1 Prevention of Rhesus Alloimmunization | Article | GLOWM

  https://www.glowm.com/article/heading/vol-3–elements-of-professional-care-and-support-before-during-and-after-pregnancy–prevention-of-rhesus-alloimmunization/id/412153

  Hemolytic disease of the fetus and newborn (HDFN) is characterized by maternalfetal blood incompatibility and consequent anemia provoked by maternal antibodies against the erythrocyte antigens of the fetus. […] In the past, perinatal mortality in alloimmunized pregnancies reached 50%, and HDFN accounted for about 10% of the causes of fetal and neonatal deaths. Medical advances during the past century have revolutionized the understanding of this serious condition and promoted a significant reduction of its occurrence, morbidity and mortality, although it remains a public health problem in developing countries. […] The incidence of Rh alloimmunization changed after the development of anti-D immunoglobulin prophylaxis. In US, where prophylaxis is universal, data from the National Center for Health Statistics in 2003 reported an incidence of HDFN in 6.8 of 1000 live births. In the UK, it is estimated that HDFN occurs once every 21,000 live births. However, in poorer and developing countries the benefits of prophylaxis are still not fully recognized owing to the unavailability of the drug or to the lack of adequate protocols to address this condition.

• #1 Globally, Only Half of Women Get Treatment for Rh Disease | Columbia University Irving Medical Center

  https://www.cuimc.columbia.edu/news/globally-only-half-women-get-treatment-preventable-killer-newborns

  A treatment developed over 50 years ago to prevent Rh diseasean often-fatal condition in fetuses and newbornsonly reaches half of the women in the world who need it, according to a study led by researchers at Vagelos College of Physicians and Surgeons (VPS) at Columbia University Irving Medical Center. […] A previous study estimated that complications of the disease may be linked to the deaths of at least 50,000 fetuses and 114,000 newborns worldwide annually. […] This is a global crisis in which hundreds of thousands of fetuses and newborns are at risk for complications and death due to Rh disease because of a lack of awareness about, access to, and availability of effective measures to prevent this disease. […] More than half of fetuses or newborns with Rh disease die; those with severe disease who survive may have significant brain damage.

• #1 Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels | Pediatric Research

  https://www.nature.com/articles/pr2013208

  Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden. […] Twenty-four million (18% of 134 million live births 32wk gestational age from 184 countries; uncertainty range: 2326 million) were at risk for neonatal hyperbilirubinemia-related adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000131,000), with a 24% risk for death (114,100; uncertainty range: 59,700172,000), 13% for kernicterus (75,400), and 11% for stillbirths. […] Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries.

• #1

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2024/04000/prevalence_of_fetomaternal_rhesus_incompatibility.14.aspx

  Fetomaternal Rhesus incompatibility is a medical condition that affects the pregnant woman [of blood group (A, B, AB, O) and a negative Rhesus] and the foetus (of positive Rhesus). The objective of this study is to determine the prevalence and to present the clinical characteristics of fetomaternal Rhesus incompatibility in a tertiary care hospital. […] Fetomaternal Rhesus incompatibility remains a major problem of maternal health because it is likely to lead to the formation of antibodies in women, which by crossing the placental barrier, they destroy red blood cells and thus cause serious complications. […] Fetomaternal Rhesus incompatibility (FMRhI) is a medical problem to be feared in pregnant women and in the foetus during the second pregnancy (or a subsequent pregnancy), and it can lead to the destruction of the red blood cells of the foetus often causing anaemia, jaundice, brain damage and in utero death in the foetus and abortion, miscarriage in the mother.

• #1

  https://www.nhs.uk/conditions/rhesus-disease/diagnosis/

  Rhesus disease is usually diagnosed during the routine antenatal checks and tests you’re offered during pregnancy. […] If you’re RhD negative, your blood will be checked for the antibodies (known as anti-D antibodies) that destroy RhD positive red blood cells. […] If anti-D antibodies are detected in your blood during pregnancy, there’s a risk that your unborn baby will be affected by rhesus disease. For this reason, you and your baby will be monitored more frequently than usual during your pregnancy. […] If your baby is at risk of developing rhesus disease, they’ll be monitored by measuring the blood flow in their brain. […] If a Doppler ultrasound shows your baby’s blood is flowing faster than normal, a procedure called foetal blood sampling (FBS) can be used to check whether your baby is anaemic (iron deficiency anaemia). […] If you’re RhD negative, blood will be taken from your baby’s umbilical cord when they’re born. This is to check their blood group and see if the anti-D antibodies have been passed into their blood. This is called a Coombs test.

• #1 Prevention of Rhesus (Rh) disease of newborns in Pakistan | The Morris Lab | SickKids | The Morris Lab

  https://lab.research.sickkids.ca/morris/ongoing-research/prevention-of-rhesus-rh-disease-of-newborns-in-pakistan/

  The availability of easy-to-use, portable, and affordable technologies can bring Rh testing to rural hard-to-reach communities in LMICs. […] The following characteristics of feasibility were explored: acceptance of the point-of-care test by pregnant women; the ability of lady health visitors to administer the point-of-care test and interpret the results; administration of RhIg prophylaxis by lady health visitors; and acceptability of RhIg by pregnant women. […] Moreover, knowledge regarding Rh disease and its consequences was assessed at enrolment and exit from the study among pregnant women, lady health visitors and other health care professionals and the prevalence of Rh(D)-negative blood groups in the study population was determined. […] Finally, the miscarriage, stillbirth, and neonatal mortality rates were determined and compared among Rh(D)-positive and Rh(D)-negative participants.

• #1 Globally, only half of women get treatment for preventable killer of newborns | EurekAlert!

  https://www.eurekalert.org/news-releases/602694

  The study found an annual worldwide gap of more than 2.5 million doses below the minimum recommended threshold for preventing Rh disease. […] In particular, in 100 countries, fewer than 80% of pregnant women who required the therapy received a dose after delivery. […] The biggest shortfalls occur in South Asia and Sub-Saharan Africa: Both regions have a high incidence of neonatal deaths due to complications of Rh disease, but virtually no Rh(D) immunoglobulin was dispensed. […] The researchers found that none of the regions studied had acceptable levels of adherence to recommended guidelines for preventing Rh disease. […] „A variety of factors, including lack of awareness of Rh incompatibility, limited availability of the therapy, and other health care priorities, play a role in hindering access to this life-saving therapy around the world,” Spitalnik says. […] Now that we have a better understanding of these gaps in treatment, we can begin to address them on a regional level.

• #1 Hemolytic disease of the fetus and newborn due to Rh(D) incompatibility: A preventable disease that still produces significant morbidity and mortality in children | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235807

  The gap between IgG anti-Rh(D) supply and demand is large in low income countries, and in high income countries, immunoprophylaxis for maternal Rh(D) sensitization also falls below the optimum threshold required to guarantee complete prevention. […] The enormous lack of prevention identified in the current study should be regarded as a global emergency due to a lack of maternal accessibility to IgG anti-Rh(D).

• #1 Consortium for Universal Rh disease Elimination (CURhE) | Division of Neonatal and Developmental Medicine | Stanford Medicine

  https://med.stanford.edu/content/sm/neonatology/Research/POTR/consortium-for-universal-rh-disease-elimination–curhe-.html

  Every year hundreds of thousands of babies, especially across Africa and Asia, are injured or die of Rh disease because their mothers were not given one or two simple injections just before or after giving birth. […] Rh disease has been virtually eliminated in wealthier nations, thanks to a simple and inexpensive prophylactic immunization developed almost fifty years ago. […] But the tragedy continues in much of Africa, Asia and Eastern Europe, simply because of a lack of awareness, education, and/or infrastructure. […] Millions of babies have died in these countries needlessly. […] In Nigeria alone, each year over 300,000 women are at risk; in India, 985,000. […] CURhE launches collaboration with Nigeria’s Federal Ministry of Health. […] The knowledge, talent and resources of this coalition will allow accurate identification of the Rh disease problem in various countries, effective collaboration with local government and health officials, creative awareness campaigns, and affordable delivery of the needed prophylactic treatment.

• #1

  https://link.springer.com/article/10.1007/s12288-020-01367-9

  Many authors have reported poor prognostic value of anti-D antibody titer in the setting of Hemolytic Disease of Fetus and Newborn (HDFN). […] Therefore, we planned this study to evaluate the prevalence and prognostic value of IgG subtypes in the setting of Rh HDFN. […] 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 multiparameter protocol for more accurate prediction HDFN severity to ensure timely referral and intervention.

• #1

  https://journals.lww.com/njcp/fulltext/2012/15040/the_prevalence_of_rhesus_negativity_among_pregnant.6.aspx

  In pregnancy, Rh D negative women whose husbands are Rh D positive need adequate counseling on the etiology of Rh D iso-immunization during the antenatal period to prevent hemolytic disease of the newborn. […] This study shows that Rh D iso-immunization is a rare cause of neonatal jaundice among neonates in Nigeria as previously documented. […] The contribution of Rh D iso-immunization from this study to perinatal mortality at the UNTH Enugu is 0.7 per 1000 births. […] There is need for proper public education about this preventable disease. Obstetricians, Hematologists, and Neonatologists also need to put in place a proper protocol for the management of Rh D negative pregnant women to prevent Rh D iso-immunization and to properly care for affected children.

• #1 Rh disease in Mexico: evaluating regional and institutional differences in treatment availability and disease management | Blood Transfusion

  https://www.bloodtransfusion.it/bt/article/view/750

  Rh disease occurs following maternal alloimmunization, which can develop due to RhD blood group antigen incompatibility between a mother and her fetus. […] Despite developing robust clinical protocols for effective immunoprophylaxis over the last 50+ years, a significant global burden of Rh disease still exists, particularly in low/middle-income countries such as Mexico. […] Significant variations in prevention and treatment were found within the Mexican healthcare system, particularly, with regard to providing anti-RhD immunoglobulin to prevent alloimmunization, which is critically important for preventing Rh disease. […] This study highlights differences in the Mexican healthcare system in preventing and treating Rh disease. Closing the gap in the availability of anti-RhD immunoglobulin should take priority in future efforts aimed at providing equitable care, because this will lead to the more preferable outcome of preventing Rh disease, rather than forcing patients to seek out more complex measures for treating Rh disease after it develops.

• #1 Rhesus negative blood and pregnancy: what you need to know | NCT

  https://www.nct.org.uk/information/pregnancy/body-pregnancy/rhesus-negative-blood-and-pregnancy-what-you-need-know

  The pregnant woman or person will be offered a test for their blood group at the initial booking appointment (NICE, 2021). […] In the UK around 85 in 100 people are rhesus positive, so around 15 in 100 are rhesus negative (NHS, 2021). […] Rhesus disease is rare, largely preventable, and almost always treatable. […] If the woman or birthing person is rhesus negative they will be offered one or two injections of Anti-D immunoglobin in pregnancy. […] If a baby is at risk of rhesus disease, extra monitoring will be offered. […] At around 12 weeks of pregnancy, the babys blood group can be found by testing the mother or birthing parents blood. […] Babies in the womb with rhesus disease will be monitored regularly. […] If the mother or birthing parent is rhesus negative, blood will be taken from the umbilical cord when the baby is born.

• #2 Prevention of Rhesus (Rh) disease of newborns in Pakistan | The Morris Lab | SickKids | The Morris Lab

  https://lab.research.sickkids.ca/morris/ongoing-research/prevention-of-rhesus-rh-disease-of-newborns-in-pakistan/

  Rhesus (Rh) hemolytic disease is a preventable disease of the newborn that is caused by an incompatibility between maternal and fetal red blood cells. […] Despite the availability of effective screening and prevention strategies that have contributed to the near eradication of Rh disease in high-income countries, the burden of Rh disease remains disproportionately high in low- and middle-income countries (LMICs). […] Globally, 373,300 live births, or 276 babies per 100,000 live births, were estimated to be affected by Rh disease in 2010. […] The prevalence of the disease is estimated to be greatest in countries with neonatal mortality rates equal to or greater than 15 newborn deaths per 1000 live births. […] The first step towards preventing Rh disease of the newborn is the early identification and prophylactic treatment of Rh(D)-negative women with two doses of anti-D immunoprophylaxis (RhIg).

• #2 Guidelines for Rhesus Disease Prevention | Article | GLOWM

  https://www.glowm.com/article/heading/vol-16–the-prevention-and-management-of-rh-disease–guidelines-for-rhesus-disease-prevention/id/418863

  Introduction of anti-Rh(D) immunoglobulin more than 50 years ago, has only resulted in a 50% decrease of Rhesus (Rh) Disease globally, due to a low uptake of this prophylaxis. […] However, recent data have shown that, in approximately 50% of eligible cases worldwide, on an annual basis, no anti-Rh(D) immunoglobulin is administered. […] It has been estimated that Rh Disease still results in more than 160,000 perinatal deaths and 100,000 cases of disability annually; only a 50% reduction as compared to the era before immunoglobulin administration. […] In 2021 the Federation of Gynecology and Obstetrics (FIGO) has published guidelines on the prevention of Rh Disease by immunoprophylaxis, considering the cost effectiveness of the different dose regimens and prioritizing its administration by indication.

• #2 Rhesus immunisation in Australia | NHMRCNHMRCNHMRC TaglineNHMRC Tagline

  https://www.nhmrc.gov.au/about-us/resources/impact-case-studies/rhesus-immunisation-australia

  Today, approximately 17% of women in Australia who become pregnant require Rh D immunoglobulin injections to prevent Rh disease and ensure their baby’s health. […] Lifeblood has maintained the Rh program collecting plasma from donors with anti-D for more than 50 years. There continue to be significant challenges in maintaining the supply of Rh D immunoglobulin in Australia due to the retirement of ageing donors, fewer new donors (due to fewer women developing anti-D antibodies following pregnancy or transfusion) and ethical concerns about increasing the anti-D levels in current donors. […] Following a systematic review of evidence and consensus by a multidisciplinary committee, NIPT for fetal RHD blood group genotype for all Rh D negative pregnancies in Australia was recommended in the Guideline for the prophylactic use of Rh D immunoglobulin in pregnancy care.

• #2 Globally, only half of women get treatment for preventable killer of newborns | EurekAlert!

  https://www.eurekalert.org/news-releases/602694

  The study found an annual worldwide gap of more than 2.5 million doses below the minimum recommended threshold for preventing Rh disease. […] In particular, in 100 countries, fewer than 80% of pregnant women who required the therapy received a dose after delivery. […] The biggest shortfalls occur in South Asia and Sub-Saharan Africa: Both regions have a high incidence of neonatal deaths due to complications of Rh disease, but virtually no Rh(D) immunoglobulin was dispensed. […] The researchers found that none of the regions studied had acceptable levels of adherence to recommended guidelines for preventing Rh disease. […] „A variety of factors, including lack of awareness of Rh incompatibility, limited availability of the therapy, and other health care priorities, play a role in hindering access to this life-saving therapy around the world,” Spitalnik says. […] Now that we have a better understanding of these gaps in treatment, we can begin to address them on a regional level.

• #2 Haemolytic Disease of the Fetus and Newborn (HDFN)

  https://patient.info/doctor/haemolytic-disease-of-the-fetus-and-newborn

  The incidence of haemolytic disease of the newborn (HDN) depends on the proportion of the population who are RhD negative; 15% of White populations (North Americans and Europeans) are found to be Rh-negative, while only 4%-8% of African and 0.1%-0.3% of Asian populations have the Rhesus negative blood group. Before immunoprophylaxis was available, HDN affected 1% of all newborns and was responsible for the death of one baby in every 2,200 births. […] Anti-D prophylaxis (mostly administered postnatally) and advances in neonatal care have reduced the frequency of HDN by almost a factor of 10 to 1 in 21,000 births. Deaths attributed to RhD alloimmunisation fell from 46/100,000 births before 1969, to 1.6/100,000 in 1990. This may not be entirely attributable to immunoglobulin; changes in abortion rates and racial composition may also play a part. One American study quoted a prevalence of RhD alloimmunisation of 6 in 1,000 births and suggests that this should now be considered a rare condition.

• #2 Globally, only half of women get treatment for preventable killer of newborns | EurekAlert!

  https://www.eurekalert.org/news-releases/602694

  Only half of pregnant women worldwide who need a treatment developed over 50 years ago to prevent Rh disease–an often-fatal condition in fetuses and newborns that is now exceedingly rare in the United States and Western Europe–actually receive it, finds a study led by researchers at Vagelos College of Physicians and Surgeons (VPS) at Columbia University Irving Medical Center. […] A previous study estimated that complications of the disease may be linked to the deaths of at least 50,000 fetuses and 114,000 newborns worldwide annually. […] More than half of fetuses or newborns with Rh disease die; those with severe disease who survive may have significant brain damage. […] The burden of Rh disease in lower-income countries is not well known; the most recent estimates are based on reported rates of neonatal complications associated with Rh incompatibility.

• #2 LSHTM LSHTM Research Online

  https://researchonline.lshtm.ac.uk/1440281/

  BACKGROUND: Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden. […] Twenty-four million (18% of 134 million live births 32 wk gestational age from 184 countries; uncertainty range: 23-26 million) were at risk for neonatal hyperbilirubinemia-related adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800-477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000-131,000), with a 24% risk for death (114,100; uncertainty range: 59,700-172,000), 13% for kernicterus (75,400), and 11% for stillbirths. […] Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. […] Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries.

• #2 Consortium for Universal Rh disease Elimination (CURhE) | Division of Neonatal and Developmental Medicine | Stanford Medicine

  https://neonatology.stanford.edu/Research/POTR/consortium-for-universal-rh-disease-elimination–curhe-.html

  Every year hundreds of thousands of babies, especially across Africa and Asia, are injured or die of Rh disease because their mothers were not given one or two simple injections just before or after giving birth. […] Rh disease has been virtually eliminated in wealthier nations, thanks to a simple and inexpensive prophylactic immunization developed almost fifty years ago. […] But the tragedy continues in much of Africa, Asia and Eastern Europe, simply because of a lack of awareness, education, and/or infrastructure. […] Millions of babies have died in these countries needlessly. […] CURhE launches collaboration with Nigeria’s Federal Ministry of Health. […] The knowledge, talent and resources of this coalition will allow accurate identification of the Rh disease problem in various countries, effective collaboration with local government and health officials, creative awareness campaigns, and affordable delivery of the needed prophylactic treatment.

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