Guideline No. 448: Prevention of Rh D Alloimmunization.

OBJECTIVE: This guideline provides recommendations for the prevention of Rh D alloimmunization (isoimmunization) in pregnancy, including parental testing, routine postpartum and antepartum prophylaxis, and other clinical indications for prophylaxis. Prevention of red cell alloimmunization in pregnancy with atypical antigens (other than the D antigen), for which immunoprophylaxis is not currently available, is not addressed in this guideline. TARGET POPULATION: All Rh D-negative pregnant individuals at risk for Rh D alloimmunization due to potential exposure to a paternally derived fetal Rh D antigen. OUTCOMES: Routine postpartum and antepartum Rh D immunoprophylaxis reduces the risk of Rh D alloimmunization at 6 months postpartum and in a subsequent pregnancy. BENEFITS, HARMS, AND COSTS: This guideline details the population of pregnant individuals who may benefit from Rho(D) immune globulin (RhIG) immunoprophylaxis. Thus, those for whom the intervention is not required may avoid adverse effects, while those who are at risk of alloimmunization may mitigate this risk for themselves and/or their fetus. EVIDENCE: For recommendations regarding use of RhIG, Medline and Medline in Process via Ovid and Embase Classic + Embase via Ovid were searched using both the trials and observational studies search strategies with study design filters. For trials, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects via Ovid were also searched. All databases were searched from January 2000 to November 26, 2019. Studies published before 2000 were captured from the grey literature of national obstetrics and gynaecology specialty societies, luminary specialty journals, and bibliographic searching. A formal process for the systematic review was undertaken for this update, as described in the systematic review manuscript published separately. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the SOGC's modified GRADE approach. See Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: The intended users of this guideline include prenatal care providers such as obstetricians, midwives, family physicians, emergency room physicians, and residents, as well as registered nurses and nurse practitioners. TWEETABLE ABSTRACT: An updated Canadian guideline for prevention of Rh D alloimmunization addresses D variants, cffDNA for fetal Rh type, and updates recommendations on timing of RhIG administration. SUMMARY STATEMENTS: RECOMMENDATIONS.

Noninvasive Fetal RhD Blood Group Genotyping: A Systematic Review of Economic Evaluations.

OBJECTIVE: Noninvasive fetal rhesus D (RhD) blood group genotyping may prevent unnecessary use of anti-D immunoglobulin (RhIG) in non-alloimmunized RhD-negative pregnancies and can guide management of alloimmunized pregnancies. We conducted a systematic review of the economic literature to determine the cost-effectiveness of this intervention over usual care. DATA SOURCES: Systematic literature searches of bibliographic databases (Ovid MEDLINE, Embase, and Cochrane) until February 26, 2019, and auto-alerts until October 30, 2020, and of grey literature sources were performed to retrieve all English-language studies. STUDY SELECTION: We included studies done in serologically confirmed non-alloimmunized or alloimmunized RhD-negative pregnancies, comparing costs and effectiveness of the intervention versus usual care. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data from the eligible studies and assessed their methodological quality (risk of bias) using the Quality of Health Economic Studies (QHES) and Drummond tools. We narratively synthesized findings. Our review included 8 economic studies that evaluated non-invasive fetal RhD genotyping followed by targeted RhIG prophylaxis in non-alloimmunized pregnancies. Five studies further considered a subsequent alloimmunized pregnancy. The cost-effectiveness of the intervention versus usual care (e.g., universal RhIG or prophylaxis conditional on results of paternal testing) for non-alloiummunized pregnancies was inconsistent. Two studies indicated greater benefits and lower costs for the intervention, and another 2 suggested a trade-off. In 4 studies, the intervention was less effective and costlier than alternatives. Three studies were determined to be of high quality by both tools. Two of these studies favoured the intervention, and one assessed benefits in quality-adjusted life-years. No study clearly examined the cost-effectiveness of repetitive use of fetal genotyping in multiple non-alloimmunized or alloimmunized pregnancies. The cost of genotyping was the most influential parameter. CONCLUSION: The cost-effectiveness of noninvasive fetal RhD genotyping for non-alloimmunized pregnancies varies between studies. Potential savings from targeted management of alloimmunized pregnancies requires further research.

Very Prolonged Anti-D: Confusion Surrounding Alloimmunization After Extra Rh Immunoglobulin: A Case Report.

BACKGROUND: Rh immunoglobulin (RhIg) is usually detectable a maximum of 12 to 14 weeks after administration. Positive antibodies beyond this time frame suggests alloimmunization. CASE: A woman had three pregnancies over a 6-month period, with two first-trimester losses. She received RhIg in the first pregnancy but not in the second. Two months after the second loss, in her third pregnancy, she received RhIg at week 6 due to first-trimester bleeding. She was subsequently anti-D antibody positive up to week 28 with antibodies too low to titre, leading to confusion about whether alloimmunization had occurred. CONCLUSION: Rh Ig administration led to positive anti-D antibodies lasting 22 weeks, suggesting keeping this differential diagnosis in mind when suspecting alloimmunization with positive antibodies at levels too low to titre.

Discordant intrauterine transfusion in dichorionic twin pregnancy with Rh isoimmunization.

Discordant intrauterine transfusion (IUT) in twin pregnancy with Rh isoimmunization is uncommon and complicated. We report a gravida 3, para 2 woman with a dichorionic diamniotic (DCDA) twin pregnancy and two fetuses received discordant transfusions. Middle cerebral artery peak systolic velocity (MCA-PSV) was used to evaluate the anemic degree in each foetus. IUT was performed 3 times in twin A and 4 times in twin B to reverse foetal anaemia. Transfusions were distinct due to the different tolerance to IUT, and the procedure could be continued in one foetus even if the other one underwent complications. Two male babies were born at 36 weeks of gestation and were given different treatments after birth. Twins were subsequently healthy after 2 years of follow up. The discordant IUT was due to the different tolerance to transfusion in the DCDA twins. Zygosity is important for the management and treatment of haemolytic anaemia in twin pregnancies.

Non-RhD alloimmunization in pregnancy: an updated review.

RhD alloimmunization in pregnancy is still the main cause of hemolytic disease of the fetus and neonate (HDFN). Nevertheless, there are other antigens that may be associated with the occurrence of this phenomenon and that have been growing in proportion, given that current prevention strategies focus only on anti-RhD antibodies. Although not widespread, the screening and diagnostic management of the disease caused by these antibodies has recommendations in the literature. For this reason, the following review was carried out with the objective of listing the main red blood cell antigen groups described - such as Rh, ABO, Kell, MNS, Duffy, Kidd, among others - addressing the clinical importance of each one, prevalence in different countries, and recommended management when detecting such antibodies during pregnancy.

Double/Triple Intrauterine Blood Transfusion in Rh-isoimmunized Anemic Fetuses in Multiple Pregnancies with Favorable Outcome.

Background: Multiple pregnancies have increased with the use of assisted reproduction, and we expect more women reporting with Rh isoimmunization among multiple gestation in near future. Intrauterine transfusion in singleton itself is technically difficult and requires a lot of skill and precision. Performing double/triple transfusion in twins/triplets is expected to be more demanding. Aim: To create awareness on the technical difficulties encountered in intrauterine transfusion in twins and triplets. Methodology: We report a case series of four Rh-isoimmunized twins/triplets in 5 years who presented with severe anemia requiring intrauterine transfusion. Results: Each of the four sets of cases had their own intricacies that needed to be pondered before tackling them as not much was available in the literature. In Case 1, the first twin intrauterine transfusion in our 20-year-long experience, the difficulty in the approach to the first twin due to a posteriorly placed placenta has been highlighted. Case 2 was rare due to the concomitant presence of atypical antibodies in the mother in addition to Rh-D isoimmunization that made it difficult to cross match any donor blood for intrauterine transfusion. The third case was exclusive due to its monochorionic-diamniotic nature of the twins where the impact of inter-twin anastomosis on the transfusion was to be taken into consideration. Fourth case was a triplet gestation where the difficulty of which cord to be assigned to which fetus, the crowded space for intervention, as well as the risk of prolonged operative time and associated risk of preterm/premature rupture of membranes were our concern. Conclusion: Intrauterine transfusion (IUT) in twins/triplets is challenging. Difficulties encountered during IUT in multifetal gestation are due to different or uncertain chorionicity, intraplacental anastomosis between vessels, different degree of anemia in twins, difficult to ascertain cord-fetus relationship and difficulty to reach placental insertion site due to crowding by multiple fetal parts.

Use of prophylactic phototherapy for RhD neonatal disease in a referral service.

OBJECTIVE: This study aimed to describe the effect of prophylactic phototherapy in the treatment of infants with Neonatal Hemolytic Disease. METHOD: A retrospective cohort study was carried out with 199 RhD-positive infants, born to RhD-negative mothers, alloimmunized for RhD antigen, between January 2009 and December 2018. RESULTS: The incidence of exchange transfusions in the study population was 9.5%, with a mean maximum bilirubin value of 11.3 mg % (± 4.3mg %). Bilirubin's maximum peak was achieved with a mean of 119.2 life hours (± 70.6h). CONCLUSION: The low incidence of exchange transfusion, the extended maximum bilirubin peak for later ages, and the low mean of the maximum bilirubin values may indicate a positive effect of prophylactic phototherapy in the treatment of this disease. Further studies must be carried out to confirm these findings.

Recombinant anti-D for prevention of maternal-foetal Rh(D) alloimmunization: a randomized multi-centre clinical trial.

OBJECTIVE: To compare the efficacy and safety of recombinant anti-D (R-anti-D) with conventional polyclonal anti-D (Poly anti-D) in preventing maternal-fetal rhesus D (RhD) alloimmunization and to investigate the immunogenicity of R-anti-D. METHODS: This was a randomized, open-label, multi-center clinical trial conducted in RhD-negative pregnant women who did not receive antenatal anti-D who delivered RhD-positive babies and showed negative indirect Coombs tests (ICTs) at baseline. The women were randomized in a 2:1 ratio to R-anti-D or Poly anti-D groups and were administered 300 mcg (IM) of the corresponding drug within 72 hours of delivery. ICT was performed 72 hours, 90 days, and 180 days after anti-D injection. Serum samples were collected to check for the development of antibodies against R-anti-D at days 90 and 180, using bridging enzyme-linked immunosorbent assay. The proportion of subjects who had positive ICT results at days 90 and 180 were compared between the groups using Fisher's exact test. RESULTS: A total of 144 women were randomized to the R-anti-D group and 71 to the Poly anti-D group. Three women in the R-anti-D and none in the Poly anti-D group had a positive ICT result at day 90. No woman in either group had positive ICT result at day 180. Both drugs were well tolerated with only 4 reports of adverse events in each group-all were mild, non-serious, and resolved without sequelae. No subject developed antibodies against R-anti-D. CONCLUSION: The studied R-anti-D is comparable in efficacy to conventional Poly anti-D and is safe and non-immunogenic.Trial Registration: Clinical Trials Registry of India Identifier: Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2017/03/008101.

Rhesus Isoimmunization: Late-onset Hemolytic Disease of the Newborn Without Jaundice.

Rhesus (Rh) isoimmunization commonly presents with anemia and jaundice of varying intensity in the early postnatal period and is usually treated with phototherapy and exchange transfusion. Rarely, babies with mild or no symptoms at birth may present later with severe hemolytic anemia. This report describes a newborn infant with no postnatal jaundice who presented during the second week of life with severe anemia. These findings indicate the importance of regular follow-up and close monitoring of Rh-isoimmunized infants during the first two months of life for delayed onset anemia.

Fetal anemia: Diagnosis and management.

Fetal anemia has been known for many years as a dangerous complication of pregnancy. Its most common causes are maternal alloimmunization and parvovirus B19 infection, although it can be associated with many different pathological conditions including fetal aneuploidies, vascular tumors, and arteriovenous malformations of the fetus or placenta and inherited conditions such as alpha-thalassemia or genetic metabolic disorders. Doppler ultrasonographic assessment of the peak velocity of systolic blood flow in the middle cerebral artery for the diagnosis of fetal anemia and intravascular intrauterine transfusion for its treatment are the current practice standards. Live birth rates as high as 95% have been reported in recent years. The additional role of intravenous immunoglobulin therapy and the long-term consequences of the condition are the subjects of active ongoing research.

Perinatal Outcome After Intrauterine Transfusion in Rh Isoimmunized Mothers.

OBJECTIVE: The objective of the study was to assess the fetal outcome after receiving intrauterine transfusion (IUT) in Rh-isoimmunized pregnancy in a tertiary care center. STUDY DESIGN: This was a retrospective observational descriptive study in which all Rh-negative gravidas with isoimmunization warranting IUTs (40 patients) were analyzed during the period from January 1, 2010 to October 31, 2015. Primary outcome variables were fetal outcomes and procedural-related factors. RESULTS: Forty pregnancies (13-hydropic, 27-non-hydropic) required 74 IUTs. IUT was performed at gestational age of 15.4-33 weeks when indicated. The amount of blood transfused ranged from 4 to 110 ml. There were two sudden intrauterine fetal deaths during the procedure, four post-procedure intrauterine fetal deaths in fetuses with severe hydrops, and three neonatal deaths. The overall survival rate was found to be 77.5%. CONCLUSION: IUT was found to be an effective therapy in correcting anemia in fetuses of Rh isoimmunized mothers. Early diagnosis of fetal anemia and intrauterine blood transfusion by an experienced fetal medicine specialist is very important for the perinatal outcome.

Intravenous Immunoglobulins as Adjunct Treatment to Phototherapy in Isoimmune Hemolytic Disease of the Newborn: A Retrospective Case-Control Study.

BACKGROUND: Isoimmune hemolytic disease is a major cause of neonatal severe indirect hyperbilirubinemia that requires phototherapy or exchange transfusion which is an invasive procedure to avoid brain injury. Administration of intravenous immunoglobulin (IVIG) is used as an adjunct treatment to phototherapy in order to decrease the rate of exchange transfusion. METHODS: This retrospective case-control study aimed to describe the safety and efficacy of IVIG therapy in newborns with isoimmune hemolytic disease and to compare their clinical outcomes to those of a control group who were treated only with phototherapy. Criteria for IVIG treatment were variable; when phototherapy threshold was reached or when exchange transfusion level was approached, using either indication is based on the attending discretion. RESULTS: Ninety-four infants were included in the IVIG group, compared to 108 infants in the control group. Most of the included infants were term infants and most common cause was ABO incompatibility. There were no side effects documented in all the included infants. The IVIG group had more severe hemolysis with average highest bilirubin of 14.6 ± 3.7 mg/dL in the IVIG group versus 12.6 ± 3 in the control group (P = 0.0001). Complication of hemolysis was seen more in the IVIG group with higher rate of rebound hyperbilirubinemia, blood transfusion and exchange transfusion. CONCLUSIONS: IVIG use as an adjunct treatment to phototherapy in isoimmune hemolytic disease of the newborns is safe. The favorable results of the phototherapy only group were supportive of using selective criteria for administration of IVIG in neonates with isoimmune hemolytic disease.

Rh-incompatible hemolytic disease of the newborn in Hefei.

BACKGROUND: Anti-D antibody is not the common cause of Rh-isoimmunization in Chinese neonatal jaundice. Recent change in national population policy has followed by an increase in Rh-isoimmunization related hemolytic disease of the newborn (HDN). Unfortunately, regional status of Rh-HDN is unavailable. We hypothesize that Rh-HDN in our region is most commonly due to anti-E antibody. AIM: To investigate the prevalence of hemolytic disease of the newborn due to Rh-isoimmunization in Hefei City. METHODS: Retrospective review of data obtained from Children's Hospital of Anhui and Hefei Blood Center between January 2017 and June 2019. Status of minor blood group antibody was studied in the corresponding mothers. RESULTS: Totally 4138 newborns with HDN admitted during the study period and 116 (2.8%) received blood exchange transfusion (BET). Eighteen newborns (0.43%) with proven Rh-incompatible HDN were identified. All were not the first-born baby. Thirteen mothers were RhD (+) (72%) and five were RhD (-). The distribution of Rh-related antibodies in mothers was ten anti-E (55%), five anti-D (27%), and for one anti-C, anti-c, and anti-E/c (6%) each. Thirteen (72.2%) were qualified for BET, relative risk for BET was 28.9 as compared to other types of HDN, but only 10 received due to parenteral refusal. All (100%) RhD related HDN received BET which is not significantly different from RhE related HDN (81.8%). CONCLUSION: As expected, all Rh-incompatible HDN newborns were not the first-born. Contrary to the Caucasian population, anti-D induced HDN is not the most common etiology. In our region, anti-E (11/18, 61%) is the most common cause of Rh-HDN.

Non-RhD alloimmunization in pregnancy: an updated review

Abstract RhD alloimmunization in pregnancy is still the main cause of hemolytic disease of the fetus and neonate (HDFN). Nevertheless, there are other antigens that may be associated with the occurrence of this phenomenon and that have been growing in proportion, given that current prevention strategies focus only on anti-RhD antibodies. Although not widespread, the screening and diagnostic management of the disease caused by these antibodies has recommendations in the literature. For this reason, the following review was carried out with the objective of listing the main red blood cell antigen groups described — such as Rh, ABO, Kell, MNS, Duffy, Kidd, among others — addressing the clinical importance of each one, prevalence in different countries, and recommended management when detecting such antibodies during pregnancy.

Use of prophylactic phototherapy for RhD neonatal disease in a referral service

Abstract Objective: This study aimed to describe the effect of prophylactic phototherapy in the treatment of infants with Neonatal Hemolytic Disease. Method: A retrospective cohort study was carried out with 199 RhD-positive infants, born to RhD-negative mothers, alloimmunized for RhD antigen, between January 2009 and December 2018. Results: The incidence of exchange transfusions in the study population was 9.5%, with a mean maximum bilirubin value of 11.3 mg % (± 4.3mg %). Bilirubin's maximum peak was achieved with a mean of 119.2 life hours (± 70.6h). Conclusions: The low incidence of exchange transfusion, the extended maximum bilirubin peak for later ages, and the low mean of the maximum bilirubin values may indicate a positive effect of prophylactic phototherapy in the treatment of this disease. Further studies must be carried out to confirm these findings.

Descripción de una población de embarazadas con incompatibilidad Rh (D) / Description of a population of pregnant women with Rh (D) incompatibility

Resumen OBJETIVO: Describir los desenlaces maternos y perinatales en embarazadas con incompatibilidad Rh D. MATERIALES Y MÉTODOS: Estudio de cohorte retrospectiva efectuado en la Unidad Materno Infantil de Medellín, Colombia, en pacientes embarazadas atendidas entre 2013 y 2018 con incompatibilidad Rh. Se realizó un muestreo no probabilístico de casos consecutivos y un análisis univariado. RESULTADOS: Se incluyeron 250 pacientes con mediana de edad de 26 años y tipo de sangre O-, que fue el más prevalente (55.2%). El 49.2% de las pacientes había tenido entre 2 y 3 embarazos previos. El 88% de las pacientes no había tenido ningún evento sensibilizante durante el embarazo. El 65.2% tuvo un reporte negativo del primer Coombs y la media de semanas de embarazo al primer Coombs fue de 28. El 48% de las pacientes recibió la inmunoglobulina G anti-D a una mediana de 28 semanas de gestación. CONCLUSIÓN: El estudio confirma datos clínicos y sociodemográficos y sugiere que se requiere fortalecer la oportunidad en la captación temprana de las pacientes para el seguimiento con el Coombs y para la indicación de la profilaxis.

Abstract OBJECTIVE: To determine the maternal and fetal outcomes in pregnant women with Rh D incompatibility. MATERIALS AND METHODS: A Retrospective cohort study carried out in the Maternal and Child Unit of Medellín, Colombia, in pregnant patients attended between 2013 and 2018. RESULTS: 250 patients were included, in which the median age was 26 years. The O- blood type was the most prevalent in pregnant women with 55.2% and 49.2% of the patients had had between 2 and 3 previous pregnancies, in addition, 88% of the patients had not presented any sensitizing event during her pregnancy. 65.2% had a negative first Coombs result and the mean gestational age of the first Coombs was 28 weeks. 48% of patients received immunoglobulin G anti D at a median gestational age of 28 weeks. CONCLUSION: The present study confirms the clinical and sociodemographic data, however it suggests that it may be necessary to strengthen the opportunity in the early recruitment of patients for follow-up with Coombs and for the indication of prophylaxis.

Isoinmunización Rh en bajas respondedoras: Reporte de caso / Rh Isoimmunization in Low Responders: Case Report / Isoimunização Rh em pacientes com baixa resposta: relato de caso

Introducción. La isoinmunización Rh consiste en la producción de anticuerpos maternos en una gestante Rh negativa contra los antígenos de los eritrocitos Rh positivos fetales ocasionados por una hemorragia fetomaterna. En población gestante, el 15% son Rh negativo y la severidad de la afectación fetal está relacionada con una serie de procesos inmunológicos y la historia obstétrica. Si una gestante Rh negativa con riesgo de isoinmunización no recibe profilaxis con inmunoglobulina Anti-D se inmuniza el 16% en la primera gestación, el 30% en la segunda y el 50% después de la tercera. Con este reporte de caso queremos describir el subgrupo de pacientes gestantes con isoinmunización Rh bajas respondedoras. Presentación del caso. G9P5C1A2Gem1V7 de 43 años, remitida en semana 30 de gestación por isoinmunización Rh, no recibió inmunoglobulina Anti-D durante este embarazo, ni en los anteriores ni en el posparto, reporte de Coombs indirecto de 1/4 que se eleva a 1/16, seguimiento ecográfico normal. En semana 35.3 presenta anemia fetal leve y por tratarse de un embarazo alrededor del término se finaliza por cesárea. Recién nacido con adecuado peso para la edad gestacional, quien fue dado de alta a las 72 horas con evolución satisfactoria. Discusión. Las gestantes con isoinmunización Rh bajas respondedoras se sensibilizan con altos volúmenes sanguíneos sin repercusión hemodinámica in utero, produciendo una enfermedad hemolítica fetal leve. Esta respuesta inmune es poco frecuente y está asociada a factores protectores; sin embargo, son necesarios más estudios que sustenten esta condición. Conclusiones. El control prenatal y el Coombs indirecto cuantitativo seriado son las principales herramientas para la prevención de la isoinmunización. El conocimiento de la respuesta inmunológica permite identificar el subgrupo de las bajas respondedoras que tienen una evolución clínica más leve y menor morbilidad neonatal. Palabras clave: Embarazo; Isoinmunización Rh; Eritroblastosis Fetal; Globulina Inmune RHO(D); Hidropesía Fetal.

Introduction. Rh isoimmunization consists of a Rh-negative pregnant woman producing maternal antibodies against the antigens of fetal Rh-positive erythrocytes due to fetomaternal hemorrhage. 15% of the pregnant population is Rh negative, and the severity of fetal effects is related to a series of immunological processes and the obstetric history. If a Rh-negative pregnant woman at risk of isoimmunization does not receive a prophylaxis of Anti-D immunolobulin, 16% are immunized in the first pregnancy, 30% in the second and 50% after the third. In this case report we will describe the subgroup of low responder pregnant patients with Rh isoimmunization. Case Presentation. G9P5C1A2Gem1V7, 43 years old, referred on the 30th week of pregnancy due to Rh isoimmunization. She did not receive Anti-D immunolobulin during this pregnancy, nor in her previous pregnancies, nor during postpartum. Indirect Coombs report of 1/4, which increases to 1/16. Ultrasound monitoring is normal. At week 35.3 she presented mild fetal anemia, and because the pregnancy was near its term, it was ended by cesarean section. Newborn with adequate weight considering the gestational age, who was then discharged after 72 hours with satisfactory evolution. Discussion. Low responder pregnant women with Rh isoimmunization are sensitized with high blood volumes but without hemodynamic repercussions in utero, producing a mild fetal hemolytic disease. This immune response is infrequent and is associated with protective factors; however, further studies are required to support this condition. Conclusions. Prenatal control and serialized quantitative indirect Coombs testing are the main tools for the prevention of isoimmunization. Knowledge of the immunological response enables identifying the subgroup of low responders who present a milder clinical evolution and lower newborn morbidity. Keywords: Pregnancy; Rh Isoimmunization; Erythroblastosis, Fetal; RHO(D) Immune Globulin; Hydrops Fetalis.

Introdução. A isoimunização Rh consiste na produção de anticorpos maternos em uma gestante Rh negativa contra os antígenos dos eritrócitos fetais Rh positivos causados por hemorragia fetomaterna. Na população gestante, 15% são Rh negativos e a gravidade do envolvimento fetal está relacionada a uma série de processos imunológicos e ao histórico obstétrico. Se uma gestante Rh negativa com risco de isoimunização não receber profilaxia com imunoglobulina Anti-D, imuniza-se 16% na primeira gestação, 30% na segunda e 50% após a terceira. Com este relato de caso, queremos descrever o subgrupo de pacientes gestantes com isoimunização Rh de baixa resposta. Apresentação do caso. G9P5C1A2Gem1V7, 43 anos, encaminhada na 30ª semana de gestação para isoimunização Rh, não recebeu imunoglobulina Anti-D nesta gestação, nem nas anteriores nem no puerpério, laudo de Coombs indireto de 1/4 que sobe para 1/16, acompanhamento ultrassonográfico normal. Na semana 35,3, apresentou anemia fetal leve e por se tratar de uma gestação próxima ao termo, foi interrompida por cesariana. Recém-nascido com peso adequado para a idade gestacional, que recebeu alta às 72 horas com evolução satisfatória. Discussão. Gestantes com isoimunização Rh de baixa resposta são sensibilizadas com elevados volumes sanguíneos sem repercussões hemodinâmicas in utero, produzindo doença hemolítica fetal leve. Essa resposta imune é rara e está associada a fatores protetores; no entanto, mais estudos são necessários para fundamentar esta condição. Conclusões. O controle pré-natal e o Coombs indireto quantitativo seriado são as principais ferramentas para a prevenção da isoimunização. O conhecimento da resposta imunológica permite identificar o subgrupo de pacientes com baixa resposta que apresentam evolução clínica mais branda e menor morbidade neonatal. Palavras-chave: Gravidez; Isoimunização Rh; Eritroblastose Fetal; Inmunoglobulina RHO (D), Hidropisia Fetal.

Rh isoimmunized pregnancy managed noninvasively: A report of two cases.

Pregnancy with Rh isoimmunization is a grave situation. Two women with indirect Coombs test (ICT) positive were managed conservatively with a favorable outcome. Peak systolic velocity (PSV) of middle cerebral artery (MCA) was measured every 2 weeks, and pregnancy continued till the value remained <1.5 mean of median. In one woman, the pregnancy could be prolonged to 37 weeks when delivery was induced and the neonate did not develop hyperbilirubinemia. In the second woman with bad obstetric history, when a highly positive ICT was reported, intravenous immunoglobulin (IVIG) was given in a single dose of 5 g every 2 weeks starting at 27 weeks, for a total of three doses, along with measurement of PSV of MCA. Labor could be prolonged to 34 weeks when preterm spontaneous delivery occurred. The neonate could be salvaged with exchange transfusion and IVIG. The neonate is healthy with normal tone and no evidence of kernicterus.

Hidropesía fetal y enfermedad hemolítica del feto y el recién nacido / Hydrops Fetalis and Hemolytic Disease of the fetus and the newborn. Update

Introducción: la enfermedad hemolítica del feto y el recién nacido (EHFRN) consiste en la incompatibilidad presente entre los antígenos eritrocitarios maternos y los fetales, que desencadena en la madre una reacción inmunitaria contra los eritrocitos fetales produciendo su destrucción. La complicación más grave es la hidropesía fetal, la cual consiste en síntomas de origen hemodinámico, derivados de una falla cardíaca por la disminución en el aporte de oxígeno o por la falta de producción de albúmina. Objetivo: realizar una revisión actualizada de la EHFRN, exponiendo principalmente la hidropesía fetal como una de sus grandes complicaciones. Metodología: se realizó una revisión bibliográfica desde 2018 hasta 2021 en bases de datos tales como Science Direct, Pubmed y Medline con base en los siguientes términos MeSH: anemia hemolítica, isoinmunización Rh, eritroblastosis fetal, hidropesía fetal. Conclusión: la EHFRN es una causa frecuente de enfermedad hemolítica grave en estos pacientes, pero gracias a la Inmunoglubulina G anti-D se ha logrado prevenir la mayoría de casos de incompatibilidad Rh. Sin embargo, la hidropesía fetal presenta una alta mortalidad, lo cual hace importante promover un diagnóstico oportuno y el uso de profilaxis

Introduction: Hemolytic disease of the fetus and newborn (EHFRN) consists of the incompatibility present between maternal and fetal erythrocyte antigens, which triggers an immune reaction in the mother against fetal erythrocytes, causing their destruction. The most serious complication is hydrops fetalis, which consists of symptoms of hemodynamic origin, derived from heart failure due to the decrease in oxygen supply or the lack of albumin production. Objective: Make an updated review of the EHFRN, exposing mainly hydrops fetalis as one of its major complications. Methodology: Bibliographic review was carried out from 2018 to 2021 in databases such as Science Direct, Pubmed and Medline based on the following MeSH terms: hemolytic anemia, Rh isoimmunization, erythroblastosis fetalis, hydrops fetalis. Conclusion: EHFRN is a frequent cause of severe hemolytic disease in these patients; but thanks to the anti-D Immunoglobulin G, the majority of cases of Rh incompatibility have been prevented. However, hydrops fetalis has a high mortality rate, which makes it important to promote timely diagnosis and the use of prophylaxis

Antenatal Maternal Serum IAT Titer and Fetal Outcome in Rh Isoimmunized Pregnancies.

The incidence of Rh negativity in India is about 1-5 % and the rate of Rh sensitization to be approximately 0.79 % of live births. This study evaluated the role of antenatal maternal serum Indirect Antiglobulin Test (IAT) titre in predicting the feto-neonatal outcome. The study was conducted from Jan 2007 to Dec 2012 at our centre in Pune, Maharashtra, India. This study reports our experience with 75 IUTs carried out for 42 cases of severe Rh isoimmunization. IAT was performed by ID gel cards and test tube method was utilized for titration. Results were analysed by odds ratio (OR) with 95 % Confidence Interval. IAT titre was found to have a direct correlation with the maternal parity, requirement of number of IUT's and adverse fetal outcome. Of the 42 cases of severe Rhisoimmunization who underwent IUT, 11 (26.2 %) had hydropic fetus resulting in 08 (73 %) live babies, two intrauterine and one neonatal death. The remaining 31 (73.8 %) non-hydropic fetuses who received IUT, one intrauterine and one neonatal death were observed. In the 11 hydropic cases, who received IUTs, two intrauterine and one neonatal death were observed in which the IAT titre was ≥512, which was found statistically significant with OR of 9.77 & P value of 0.05. The overall survival rate was 37/42 (88.1 %). Severity and fetal outcome in Rh isoimmunized pregnancies, showed a significant association with antenatal maternal serum IAT titre. More the antibody titre more would be the fetal and/or neonatal severity with respect to immune hemolytic anemia. Requirement of multiple IUTs are also associated with high antenatal serum IAT titre.