anti-D Research Articles

Frequency and Prognosis of Hydrops Fetalis: A 10-Year Single-Center Experience.

Objective:The study aims to evaluate the etiological distribution and prognosis of newborn infants with hydrops fetalis (HF).Methods:All infants born in our hospital within the past 10 years and hospitalized with the diagnosis of HF were included in this retrospective descriptive study. Demographic characteristics, etiological distributions, treatment interventions, and prognosis information of the infants were recorded retrospectively. Infants with incomplete data were excluded from the study.Results:The mean gestational age of infants with HF was 33.6±3.1 weeks, and the mean birth weight was 2444±792 grams. Of the HF cases, 90.5% were born by cesarean section and the prenatal diagnosis rate was 42.9%. About 57.1% of the infants were intubated during resuscitation at birth in the delivery room. In the NICU, 81% of the cases were intubated and 71.4% received surfactant treatment. The most common HF findings were ascites (81%) and subcutaneous edema (81%). The most common interventional procedures were paracentesis (81%) and thoracentesis (52.4%). Exchange transfusion was performed in 2 cases (9.5%) due to immune HF. The mortality rate in the study group was 52.4%. Considering the etiological distribution of HF cases in the study group, three cases were diagnosed with immune HF (14.3%) and 18 cases with non-immune hydrops fetalis (NIHF) (85.7%). The underlying cause in immune HF cases was rhesus incompatibility. In cases with NIHF, idiopathic (23.8%) and cardiovascular diseases were the most common etiologies. A significant relationship was found between delivery room management and mortality. While the need for intubation in delivery room was significantly higher in non-survivors, the frequency of applying only positive pressure ventilation in the delivery room was significantly higher in survivors. While the rate of survival was 66.7% in immune HF cases, it was 44.4% in NIHF cases.Conclusion:The risk of perinatal mortality in infants with HF is high depending on the underlying cause. In this study, it was determined that HF mostly developed for non-immune reasons, prenatal diagnosis and follow-up were insufficient and the interventions performed in the delivery room were an important factor in predicting mortality in the follow-up of neonates with HF.

Gendered Silence and Misdiagnosis in the Clinical Encounter: Celia de Fréine's Blood Debts and the Hepatitis C Scandal in Ireland

Gendered Silence and Misdiagnosis in the Clinical Encounter:Celia de Fréine's Blood Debts and the Hepatitis C Scandal in Ireland* Luz Mar González-Arias (bio) … a blood disorder is a whole body issue.Unanchored, migrant—blood is its own diaspora. sinÉad gleeson, constellations (37) The history of women's health care is characterized by silenced or heavily edited episodes that have contributed to the neglect of women's bodies and minds and accordingly prevented them from receiving the best possible treatments. As Hannah Devlin has contended, this prevailing attitude toward women's health has triggered "a string of health-care scandals over several decades" in which the voices of the patients have been consistently ignored. Ireland is no exception in this respect, and its history, both past and present, is punctuated by the silencing of women's voices and bodies in the clinical encounter. The death of Savita Halappanavar in October 2012 at Galway University Hospital—where, in spite of her physical distress and severe complications in the midst of a miscarriage, she was refused a termination of her pregnancy because there was still a fetal heartbeat—stands out among the recent failures of the Irish medical, religious, and political systems with respect to women, and it has left an indelible impact on the campaigns for reproductive justice in the [End Page 264] country (Holland). The CervicalCheck cancer controversy, which first emerged in 2018 and involved scores of women who received incorrect smear-test results; the brutal procedure of symphysiotomy, performed as an alternative to caesarean sections; and the hepatitis C scandal that will be the focus of this essay have also become paradigmatic examples of obstetric violence and gender imbalances in the medical history of Ireland. Celia de Fréine's collection Blood Debts, originally published in Irish as Fiacha Fola in 2004,1 and rendered into English by the author herself in 2014, is to date the only poetic articulation of the so-called hepatitis C scandal (also known as the Anti-D scandal) in Ireland. In the late 1970s about 1,600 Irish citizens, most of them women, were infected with a contaminated blood product: Anti-D immunoglobulin, also known as the Anti-D agent. The product was given to women with rhesus-negative blood who had given birth to rhesuspositive babies in order to prevent damage to the fetus in any subsequent pregnancies. This blood product was revolutionary in the prevention of rhesus disease, but it proved disastrous for the patients who received a batch manufactured in 1976 by the Irish Blood Transfusion Service Board (BTSB) from a donor who had infective hepatitis. A number of women were diagnosed with lupus, jaundice, fatigue, and a rash, but no connection between their illnesses and the toxic agent was initially established. The scandal, which has been referred to as "Ireland's greatest medical disaster" (Keane), was made public only in 1994 when evidence was provided that the BTSB had been alerted to the possibility of contamination yet had ignored the warning.2 De Fréine is "an inhabitant of liminal spaces" (Palacios-González and González-Arias 103), and her "creative force is to be found in the rich terrain between languages, genres, geographies, and literary [End Page 265] traditions" (González-Arias, "Afterword" 102). Although mainly known as a poet, she has also published numerous essays, worked successfully in opera and filmmaking, and published and produced numerous plays. Originally from Northern Ireland, she now divides her time between Dublin and Connemara; she has been inspired and influenced by English, Irish, French, and Eastern European literary traditions; she translates her own work from Irish into English, and most of her collections have appeared in dual-language format. De Fréine is a poet who upsets traditional boundaries, a characteristic that not only flavors the formal aspects of her work but also leaves its mark on the varied themes she has worked on, the volatile relationship between health and gender featuring prominently among them. In several of her collections, for instance, de Fréine has explored posttraumatic stress disorder and the demonstrations of extreme violence against women on the part of soldiers that...

Rhesus disease in Brazil: A multi-professional national survey

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.

BIND score: A system to triage infants readmitted for extreme hyperbilirubinemia

Extreme hyperbilirubinemia [EHB, total serum bilirubin (TB) >25 mg/dL]) can lead to death, acute bilirubin encephalopathy (ABE), exchange transfusion, and/or bilirubin-induced neurologic dysfunction (BIND). In specific low- to middle-income countries, an “epidemic” exists, therefore, a simplified triage management system is needed. Here, we studied a cohort of 72 infants readmitted for EHB (TB: 28.1 ± 2.5; range: 25–42 mg/dL). Of these, 15/72 (20.8%) newborns had BIND scores ≥4. Eleven (15.3%) infants with BIND scores of 4 to 6 developed moderate ABE, with 6/11 (54.5%) with TB of 28.1 ± 4.8 mg/dL having post-icteric sequelae. Eight infants (TB of 32.1 ± 3.5 mg/dL) had BIND scores >6 and developed adverse outcomes. One infant, who had Rh disease and a BIND score of 8 died. We report that the key determinants for adverse outcomes were TB >30 mg/dL and a BIND score ≥4 and may be useful for a systems approach to triage infants readmitted for EHB.

Prenatal RHD genotyping in Croatia: preliminary results.

Croatian Institute of Transfusion Medicine (CITM) implemented non-invasive fetal RHD genotyping as a request for targeted antenatal anti-D prophylaxis. The diagnostic performance of in-house RT-PCR method for fetal RHD genotyping and preliminary results are analyzed. Evaluation included results of RHD genotyping for 205 RhD negative pregnant women, 12-36th week of gestation, whose samples were received in period between 2015 and 2020. QIAsymphony SP DSP Virus Midi Kit was used for cffDNA extraction on QIAsymphony SP platform (Qiagen, Germany). Fragments of RHD exons 7 and 10 and later exon 5 were RT-PCR amplified. As internal controls, amplification of SRY gene or RASSF1A fragment and β-actin genes digested with BsTUI were used. We identified 70.72% (145/205) positive and 28.78% (59/205) negative fetal RHD genotypes. We had one inconclusive result (0.50%) due to the interference of maternal DNA with variant genotype RHD*09.02.00/01/*01N.01. When compared to newborns RhD phenotypes, no false negative and three false positive results (3/199, 1.50%) were observed. The test yielded 100% sensitivity and 95.08% specificity, while diagnostic accuracy was 98.48%. We were able to determine one case of fetal variant genotype RHD*04.04/*01N.01 inherited from the father. The negative and positive predictive test values were 100% and 97.86%, respectively. Automated cffDNA extraction and RT-PCR amplification of fetal RHD exons 5,7,10 and fragments of SRY, RASSF1A genes represents highly reliable system for determining fetal RHD status which enables targeted antenatal anti-D prophylaxis. To obtain high specificity of cffDNA extraction, strict and thoroughly cleaning procedures are required.

Next-generation sequencing of 35 RHD variants in 16 253 serologically D− pregnant women in the Finnish population

AbstractFetal RHD screening for targeted routine antenatal anti-D prophylaxis has been implemented in many countries, including Finland, since the 2010s. Comprehensive knowledge of the RHD polymorphism in the population is essential for the performance and safety of the anti-D prophylaxis program. During the first 3 years of the national screening program in Finland, over 16 000 samples from RhD− women were screened for fetal RHD; among them, 79 samples (0.5%) containing a maternal variant allele were detected. Of the detected maternal variants, 35 cases remained inconclusive using the traditional genotyping methods and required further analysis by next-generation sequencing (NGS) of the whole RHD gene to uncover the variant allele. In addition to the 13 RHD variants that have been previously reported in different populations, 8 novel variants were also detected, indicating that there is more variation of RHD in the RhD− Finnish population than has been previously known. Three of the novel alleles were identified in multiple samples; thus, they are likely specific to the original Finnish population. National screening has thus provided new information about the diversity of RHD variants in the Finnish population. The results show that NGS is a powerful method for genotyping the highly polymorphic RHD gene compared with traditional methods that rely on the detection of specific nucleotides by polymerase chain reaction amplification.

A Cross-Sectional Study of the Frequency of Rhesus Factor in the Population of Islamabad

Background: Rh is called the factor because it was first discovered in the blood of Rhesus monkeys. Rh is an antigen, a substance that stimulates the production of antibodies to fight foreign agents such as viruses, bacteria, and transplanted organs. Besides its role in blood transfusion, the D antigen is used to determine the risk of hemolytic disease of the newborn (or erythroblastosis fetalis) for Rh disease management. Method: After obtaining informed consent from the couple presented to the National Institute of Health Islamabad, blood grouping was carried out using standardized agglutination techniques. Blood samples were drawn aseptically and transferred to ethylenediaminetetraacetic acid-containing tubes. Slide agglutination testing was performed to determine Rh D (RhD). Results: A total of 111 of 116 couples had the same Rh factors; 105 couples were Rh-positive, and six couples were Rh-negative.

Exchange blood transfusion in neonates with severe hyperbilirubinemia in a lower-middle-income country: can we minimise the incidence?

Our descriptive study examines the clinical profile of referred neonates who underwent exchange blood transfusion (EBT) and identifies possible interventions at peripheral hospitals to decrease their severe hyperbilirubinemia. Among the 38 neonates enrolled, the following were identified as potential clinical gaps in management: early discharge within 24 h of birth (57%); non-availability of ABORh blood grouping (43%); lack of anti-D immunoprophylaxis (75%); pathological weight loss because of inadequate breastfeeding (42%); and low usage of phototherapy. Because of late recognition, the mean age at admission was 5.4 ± 3.3 days, levels of total serum bilirubin (TSB) were 516.4 ± 123.1 µmol/L, and acute bilirubin encephalopathy (ABE) was seen in 45% of neonates. Rh iso-immunisation (39.5%), ABO iso-immunisation (21%) and sepsis (8%) were major risk factors for severe hyperbilirubinaemia. Quality prenatal screening identifying at-risk newborns, preventing early discharge after birth, a bilirubin nomogram risk assignment before discharge and assuring early recognition of hyperbiliubinaemia by parents may well minimise the incidence of EBT.

Assay for "fetal hemoglobin levels" in erythrocytes: Impact of new In Vitro Diagnostics regulation and expanded applications in sickle cell disease management.

Assay for "fetal hemoglobin levels" in erythrocytes: Impact of new In Vitro Diagnostics regulation and expanded applications in sickle cell disease management.

Maternal intravenous immunoglobulin: A non-invasive treatment option for Rhesus D-sensitised women with previous adverse pregnancy outcomes

Background. Maternal intravenous immunoglobulin (IVIG) may delay the onset and severity of fetal anaemia in Rhesus D (RhD)- sensitised pregnancies, thereby minimising the need for intrauterine transfusion and its associated complications. Objective. To compare the pregnancy outcomes of RhD-sensitised women who received antenatal IVIG with those who did not receive antenatal IVIG. Methods. This was a retrospective cross-sectional analysis of RhD-sensitised women who attended the Wits Fetal Medicine Centre (Johannesburg) from 1 January 2008 to 31 May 2018. Criteria for maternal IVIG administration were: (i) previous adverse pregnancy outcome (early neonatal death, intrauterine fetal death or miscarriage related to RhD sensitisation), ( ii ) women with high antibody titre levels (≥1:64) in the absence of fetal anaemia; and ( iii ) rising antibody titre levels. Maternal antibody titre levels, pregnancy and neonatal outcomes were compared in women who received IVIG v. those who did not receive IVIG. Results. Of the 42 RhD-sensitised women, 14 received IVIG. A greater proportion of women experienced a decrease in antibody titres in the IVIG v. no-IVIG group (43% v. 11%, respectively; p =0.04). Nine of the 10 women in the IVIG group with a previous adverse pregnancy outcome had a successful pregnancy outcome following IVIG treatment. Conclusion. Maternal IVIG may provide a successful pregnancy outcome in RhD-sensitised women with previous adverse pregnancy outcomes related to Rh disease, or women with raised or increasing maternal antibody titre levels who present in the first or early second trimester.

Non-invasive fetal RHD genotyping: validation of the test and implementation of a screening program to guide anti-D prophylaxis

Non-invasive fetal RHD genotyping: validation of the test and implementation of a screening program to guide anti-D prophylaxis

Rhesus incompatibility in pregnancy: a case report

Introduction: Hemolytic disease of the fetus and newborn (HDFN) occurs due to the destruction of red blood cells, which the most common cause is rhesus incompatibility. This study aims to present a case of Rhesus incompatibility in pregnancy without a clinically significant effect on the baby.
 Case: A-38-years-old Indonesian woman with gravida 4 para 3 (G4P3A0), 32 weeks of gestational age came to the emergency department due to vaginal bleeding. On blood typing, she had an A-negative (A-) blood type. Her husband and all three of their children had O-positive (O+) blood type. The patient underwent a cesarean section due to recurrent antepartum hemorrhage following the total placenta previa. She gave birth to a baby girl, weighed 2,220 grams with an A-positive blood type. The hemoglobin level was 14.6 g/dL without any sign of neonatal jaundice during the first 24 hours of life.
 Conclusion: Our case illustrates a woman who did not show any sign of clinically Rhesus antigen alloimmunization. Low immunogenicity and dose-dependent response to a low fetal blood volume exposure might explain this phenomenon.

The fetal inflammatory response syndrome: the origins of a concept, pathophysiology, diagnosis, and obstetrical implications

The fetus can deploy a local or systemic inflammatory response when exposed to microorganisms or, alternatively, to non-infection-related stimuli (e.g., danger signals or alarmins). The term “Fetal Inflammatory Response Syndrome” (FIRS) was coined to describe a condition characterized by evidence of a systemic inflammatory response, frequently a result of the activation of the innate limb of the immune response. FIRS can be diagnosed by an increased concentration of umbilical cord plasma or serum acute phase reactants such as C-reactive protein or cytokines (e.g., interleukin-6). Pathologic evidence of a systemic fetal inflammatory response indicates the presence of funisitis or chorionic vasculitis. FIRS was first described in patients at risk for intraamniotic infection who presented preterm labor with intact membranes or preterm prelabor rupture of the membranes. However, FIRS can also be observed in patients with sterile intra-amniotic inflammation, alloimmunization (e.g., Rh disease), and active autoimmune disorders. Neonates born with FIRS have a higher rate of complications, such as early-onset neonatal sepsis, intraventricular hemorrhage, periventricular leukomalacia, and death, than those born without FIRS. Survivors are at risk for long-term sequelae that may include bronchopulmonary dysplasia, neurodevelopmental disorders, such as cerebral palsy, retinopathy of prematurity, and sensorineuronal hearing loss. Experimental FIRS can be induced by intra-amniotic administration of bacteria, microbial products (such as endotoxin), or inflammatory cytokines (such as interleukin-1), and animal models have provided important insights about the mechanisms responsible for multiple organ involvement and dysfunction. A systemic fetal inflammatory response is thought to be adaptive, but, on occasion, may become dysregulated whereby a fetal cytokine storm ensues and can lead to multiple organ dysfunction and even fetal death if delivery does not occur (“rescued by birth”). Thus, the onset of preterm labor in this context can be considered to have survival value. The evidence so far suggests that FIRS may compound the effects of immaturity and neonatal inflammation, thus increasing the risk of neonatal complications and long-term morbidity. Modulation of a dysregulated fetal inflammatory response by the administration of antimicrobial agents, anti-inflammatory agents, or cell-based therapy holds promise to reduce infant morbidity and mortality.

Hemolytic disease of the fetus and newborn due to Rh(D) incompatibility: A preventable disease that still produces significant morbidity and mortality in children.

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. However, with the regulatory approval, in 1968, of IgG anti-Rh(D) immunoprophylaxis to prevent maternal sensitization, the prospect of eradicating Rh disease was at hand. Indeed, the combination of antenatal and post-partum immunoprophylaxis is ~99% effective at preventing maternal sensitization to Rh(D). 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. The annual number of doses of anti-Rh(D) IgG required for successful immunoprophylaxis for these cases was then calculated and compared with an estimate of the annual number of doses of anti-Rh(D) produced and provided worldwide. 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. The global failure to provide this generally acknowledged standard-of-care to prevent Rh disease, even 50 years after its availability, contributes to an enormous, continuing burden of fetal and neonatal disease and provides a critically important challenge to the international health care system.

Rh Alloimmunisation: Current Updates in Antenatal and Postnatal Management.

In spite of advances in medical science, Rh alloimmunisation remains one of the leading causes of preventable neuro-morbidities and significant neonatal hyperbilirubinemia in lower-middle income countries. Despite availability of effective antenatal preventive strategy (Anti-D), its uptake in antenatal period is low due to ignorance. Further, once diagnosed, there is lack of adequate antenatal follow up in health care facility. Some of these cases even remain undiagnosed in antenatal period only to present as a case of severe hyperbilirubinemia and kernicterus in late neonatal period. Thus, there is an urgent need for creating awareness and educating health care professionals for early detection and timely management in both antenatal and postnatal period. Following two doses of anti-D prophylaxis (one in antenatal period and one in immediate postnatal period) the incidence of Rh alloimmunisation can reduce to <1%. It is recommended to follow all Rh alloimmunised pregnancies antenatally with serial indirect Coombs test titre (till critical titre is reached) followed by serial Doppler velocimetry of middle cerebral artery in a perinatal centre where facility for intrauterine transfusion as well as advanced neonatal care is available. Postnatal management of these infants comprises of confirmation of diagnosis, aggressive phototherapy and in selective cases, double volume exchange transfusion. With appropriate antenatal and postnatal management, the prognosis of Rh alloimmunised pregnancy remains favourable and long term outcome of Rh alloimmunised infants remain comparable with their normal counterparts.

Poly(I:C) causes failure of immunoprophylaxis to red blood cells expressing the KEL glycoprotein in mice

AbstractPolyclonal anti-D (Rh immune globulin [RhIg]) therapy has mitigated hemolytic disease of the newborn over the past half century, although breakthrough anti-D alloimmunization still occurs in some treated females. We hypothesized that antiviral responses may impact the efficacy of immunoprophylaxis therapy in a type 1 interferon (IFN)-dependent manner and tested this hypothesis in a murine model of KEL alloimmunization. Polyclonal anti-KEL immunoprophylaxis (KELIg) was administered to wild-type or knockout mice in the presence or absence of polyinosinic-polycytidilic acid (poly[I:C]), followed by the transfusion of murine red blood cells (RBCs) expressing the human KEL glycoprotein. Anti-KEL alloimmunization, serum cytokines, and consumption of the transfused RBCs were evaluated longitudinally. In some experiments, recipients were treated with type 1 IFN (IFN-α/β). Recipient treatment with poly(I:C) led to breakthrough anti-KEL alloimmunization despite KELIg administration. Recipient CD4+ T cells were not required for immunoprophylaxis efficacy at baseline, and modulation of the KEL glycoprotein antigen occurred to the same extent in the presence or absence of recipient inflammation. Under conditions where breakthrough anti-KEL alloimmunization occurred, KEL RBC consumption by inflammatory monocytes and serum monocyte chemoattractant protein-1 and interleukin-6 were significantly increased. Poly(I:C) or type I IFN administration was sufficient to cause breakthrough alloimmunization, with poly(I:C) inducing alloimmunization even in the absence of recipient type I IFN receptors. A better understanding of how recipient antiviral responses lead to breakthrough alloimmunization despite immunoprophylaxis may have translational relevance to instances of RhIg failure that occur in humans.

RHD genotyping is recommended for all patients with serological weak-D phenotypes in Asian populations – Cases with coexistence of weak-D and Asia type DEL alleles results in complete expression of D-antigen

Weak D types 1, 2, 3 and Asia type DEL (RHD 1227 G > A) can be treated as D-positive for purposes of Rho(D) immune globulin (RhIG) administration or selection of blood components for transfusion. To confirm these D variants, RHD genotyping can be used as a complementary to serologic tests. While ruling out weak D types 1,2,3 is useful in Caucasian populations, these are extremely rare in the Asian population, while Asia type DEL is relatively common. Distinguishing between true D-negative and Asia type DEL (RHD 1227 G > A) by genotyping has the same utility of distinguishing weak D types 1, 2, 3. The main difference between weak D and Asia type DEL is that the latter appears as D negative in conventional serologic methods, while the former will show positive in indirect anti-human immunoglobulin tests. RHD genotyping in apparent D-negative Asian patients has been established, yet the utility of genotyping in Asian patients with weakened D phenotypes require further investigation. We have observed cases of weak D patients with coexistence of a weak D allele and an Asia type DEL (RHD 1227 G > A) allele, we have found that antigen expression of D is as the weak D in indirect antiglobulin testing, yet all epitopes are detected with adsorption and elution assays. This is indicative of completeness of the D antigen epitope, and thus we suggest that all Asian patients with weakened D phenotypes can benefit from RHD genotyping.

Non-immune hydrops fetalis: a case series

Hydrops fetalis is a clinical condition characterized by pathological fluid accumulation in soft tissues and serous cavities of the fetus like peritoneal cavity, pleural cavity, pericardial space, and body wall edema. Hydrops fetalis is broadly classified into Immune Hydrops Fetalis (IHF) and Non-Immune Hydrops Fetalis (NIHF). Incidence of immune hydrops fetalis due to Erythroblastosis fetalis secondary to Rh Iso-immunisation has drastically reduced due to widespread use of anti-D immunoglobulin. In the last few decades, the majority of cases are identified as non-immune hydrops. It is important to determine the cause of the hydrops fetalis in order to administer optimal management of the neonate at birth. Despite recent advances the mortality of non-immune hydrops is still high. Authors report here six cases of non-immune hydrops fetalis encountered at our tertiary care hospital over last three years.

Editorial: Biographical Memoirs , Volume 68

Editorial: <i>Biographical Memoirs</i> , Volume 68

Infants affected by Rh sensitization: A 2-year Canadian National Surveillance Study.

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. 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. 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. 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.