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.

Rh hemolytic disease of the fetus and newborn is a potential risk for D-negative mothers who produce anti-D during pregnancy, which can lead to morbidity and mortality in subsequent pregnancies. To prevent this hemolytic disease, Rho(D) immune globulin (RhIG) is generally administered to D-negative mothers without anti-D at 28 weeks of gestation and shortly after delivery. However, current guidelines suggest that pregnant mothers with molecularly defined weak D types 1, 2, 3, 4.0, and 4.1 do not need RhIG as they are unlikely to produce alloanti-D when exposed to fetuses with D-positive red cells. This issue and the necessity of RHD genotyping have been extensively discussed in Western countries, where these variants are relatively common. Recent evidence indicates that women with Asian-type DEL (c.1227G>A) also do not form alloanti-D when exposed to D-positive red cells. We report that mothers with molecularly defined Asian-type DEL, similar to those with weak D types 1, 2, 3, 4.0, and 4.1, do not require RhIG before and after delivery. Collectively, this review could pave the way for the revision of international guidelines to include the selective use of RhIG based on specific genotypes, particularly in women with the Asian-type DEL.

UNASSIGNED: 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.
UNASSIGNED: To create awareness on the technical difficulties encountered in intrauterine transfusion in twins and triplets.
UNASSIGNED: We report a case series of four Rh-isoimmunized twins/triplets in 5 years who presented with severe anemia requiring intrauterine transfusion.
UNASSIGNED: 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.
UNASSIGNED: 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.

While population-level data suggest Rh immunoglobulin is unnecessary before 12 weeks\' gestation, clinical evidence is limited. Thus, guidelines vary, creating confusion surrounding risks and benefits of Rh testing and treatment. As abortion care in traditional clinical settings becomes harder to access, many people are choosing to self-manage and need to know if ancillary blood type testing is necessary.
To determine how frequently maternal exposure to fetal red blood cells (fRBCs) exceeds the most conservative published threshold for Rh sensitization in induced first-trimester abortion.
Multicenter, observational, prospective cohort study using high-throughput flow cytometry to detect circulating fRBCs in paired maternal blood samples before and after induced first-trimester abortion (medication or procedural). Individuals undergoing induced first-trimester abortion before 12 weeks 0 days\' gestation were included. Paired blood samples were available from 506 participants who underwent either medical (n = 319 [63.0%]) or procedural (n = 187 [37.0%]) abortion.
Induced first-trimester abortion.
The primary outcome was the proportion of participants with fRBC counts above the sensitization threshold (125 fRBCs/5 million total RBCs) after induced first-trimester abortion.
Among the 506 participants, the mean (SD) age was 27.4 (5.5) years, 313 (61.9%) were Black, and 123 (24.3%) were White. Three of the 506 participants had elevated fRBC counts at baseline; 1 of these patients had an elevated fRBC count following the abortion (0.2% [95% CI, 0%-0.93%]). No other participants had elevated fRBC counts above the sensitization threshold after induced first-trimester abortion. The median change from baseline was 0 fRBCs, with upper 95th and 99th percentiles of 24 and 35.6 fRBCs, respectively. Although there was a strong association between the preabortion and postabortion fRBC counts, no other baseline characteristic was significantly associated with postabortion fRBC count.
Induced first-trimester abortion is not a risk factor for Rh sensitization, indicating that Rh testing and treatment are unnecessary before 12 weeks\' gestation. This evidence may be used to inform international guidelines for Rh immunoglobulin administration following first-trimester induced abortion.

BACKGROUND: Targeted routine antenatal prophylaxis with anti-D immunoglobulin (Ig) only to RhD-negative pregnant women who carry RhD-positive fetuses (determined by fetal RHD genotyping) has reduced D-alloimmunization significantly when administered in addition to postnatal prophylaxis. Achieving high analysis sensitivity and few false-negative fetal RHD results will make RhD typing of the newborn redundant. Postnatal prophylaxis can then be given based on the result of fetal RHD genotyping. Terminating routine RhD typing of the newborns in cord blood will streamline maternity care. Accordingly, we compared the results of fetal RHD genotyping with RhD typing of the newborns.
METHODS: Fetal RHD genotyping was performed, and antenatal anti-D Ig was administered at gestational week 24 and 28, respectively. Data for 2017-2020 are reported.
RESULTS: Ten laboratories reported 18,536 fetal RHD genotypings, and 16,378 RhD typing results of newborns. We found 46 false-positive (0.28%) and seven false-negative (0.04%) results. Sensitivity of the assays was 99.93%, while specificity was 99.24%.
CONCLUSIONS: Few false-negative results support the good analysis quality of fetal RHD genotyping. Routine cord blood RhD typing will therefore be discontinued nationwide and postnatal anti-D Ig will now be given based on the result of fetal RHD genotyping.

暂无摘要。

OBJECTIVE: To summarize image quality variables for alloimmunized women at risk for fetal anemia. To investigate the association between image quality with the highest and median middle cerebral artery peak systolic velocity (MCA-PSV) at the last visit and fetal anemia based on hemoglobin.
METHODS: This study was a qualitative retrospective analysis of 192 Doppler ultrasound images used in the detection of fetal anemia in 26 alloimmunized women seen in a Minneapolis hospital over the past 3 years. Images were graded on seven criteria found in literature.
RESULTS: Of the images analyzed, 23 (12.0%) of the 192 met all seven image quality criteria. Using the highest MCA-PSV value, the sensitivity, and specificity were 55.6% and 94.1%, respectively. Using the median MCA-PSV value, the sensitivity, and specificity were 44.4% and 94.1%, respectively.
CONCLUSIONS: Only a minority of Doppler images meet all suggested image criteria. This could negatively impact the accuracy of the MCA-PSV measurements as indicated by the decreased sensitivity in our evaluations.

BACKGROUND: In neonates, rhesus D alloimmunization despite anti-D immunoglobulin prophylaxis is rare and often unexplained. Rhesus D alloimmunization can lead to hemolytic disease of the newborn with anemia and unconjugated hyperbilirubinemia. In past reports, transient congenital hyperinsulinism has been described as a rare complication of rhesus D alloimmunization. Our case report illustrates that rhesus D alloimmunization can result in a pseudosyndrome with severe congenital hyperinsulinism, anemia, and conjugated hyperbilirubinemia, despite correctly administered anti-D immunoglobulin prophylaxis.
METHODS: We report of a 36-year-old, Caucasian gravida 1, para 1 mother with A RhD negative blood type who received routine antenatal anti-D immunoglobulin prophylaxis. Her full term newborn boy presented with severe congenital hyperinsulinism, anemia, and conjugated hyperbilirubinemia up to 295 µmol/L (ref. < 9), accounting for 64% of the total bilirubin. Syndromic congenital hyperinsulinism was suspected. Examinations showed a positive direct antiglobulin test, initially interpreted as caused by irregular antibodies; diffuse congenital hyperinsulinism by 18F-DOPA positron emission tomography/computed tomography scan; normal genetic analyses for congenital hyperinsulinism; mildly elevated liver enzymes; delayed, but present bile excretion by Tc99m-hepatobiliary iminodiacetic acid scintigraphy; and cholestasis and mild fibrosis by liver biopsy. The maternal anti-D titer was 1:16,000 day 20 postpartum. Y-chromosome material in the mother\'s blood could not be identified. This could, however, not exclude late intrapartum fetomaternal hemorrhage as the cause of immunization. No causative genetic findings were deetrmined by trio whole exome sequencing. The child went into clinical remission after 5.5 months.
CONCLUSIONS: Our case demonstrates that rhesus D alloimmunization may present as a pseudosyndrome with transient congenital hyperinsulinism, anemia, and inspissated bile syndrome with conjugated hyperbilirubinaemia, despite anti-D immunoglobulin prophylaxis, possibly due to late fetomaternal hemorrhage.

The aim of this review was to systematically review the outcome of routine anti-D administration among unsensitised rhesus (RhD)-negative individuals who have an abortion. This review is registered with Prospero.
A search for all published and ongoing studies, without restrictions on language or publication status, was performed using the following databases from their inception: EBM Reviews Ovid - Cochrane Central Register of Controlled Trials, MEDLINE Ovid (Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily), Embase.com, Popline and Google Scholar. Study types included: randomised controlled trials, controlled trials, cohort and case-control studies from 1971 onwards. The population included women who undergo an abortion (induced, incomplete, spontaneous or septic abortion), medical or surgical <12 weeks, and isoimmunisation in a subsequent pregnancy. The primary outcomes were: (1) development of a positive Kleihauer-Betke test and (2) development of Rh alloimmunisation in a subsequent pregnancy.
A total of 2652 studies were screened with 105 accessed for full-text review. Two studies have been included with high bias appreciated. Both studies found few women to be sensitised in forming antibodies after an abortion. The limited studies available and heterogeneity prevent the conduction of a meta-analysis.
Rh immunoglobulin has well-documented safety. However, it is not without risks and costs, is a possible barrier to delivering efficient services, and may have limited availability in some countries. The evidence base and quality of studies are currently limited. There is unclear benefit from the recommendation for Rh testing and immunoglobulin administration in early pregnancy. More research is needed as clinical practice guidelines are varied, based on expert opinions and moving away from testing and administration at time of abortion.
There is limited evidence surrounding medical benefit of Rh testing and immunoglobulin administration in early pregnancy. Further research is needed to define alloimmunisation and immunoglobulin benefit to update standards of care. Additionally, other factors should be considered in forming clinical policies and guidelines such as costs, feasibility and impact on access to care for patients.

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.
METHODS: 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.
METHODS: We included studies done in serologically confirmed non-alloimmunized or alloimmunized RhD-negative pregnancies, comparing costs and effectiveness of the intervention versus usual care.
METHODS: 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.
CONCLUSIONS: 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.