Neonatal hemolytic disease: How should we use indirect and direct antiglobulin tests?

BACKGROUND: In newborns with hemolysis, the direct antiglobulin test (DAT) and indirect antiglobulin test (IAT) play a key role in demonstrating the presence of an immune cause. We aimed to emphasize the importance of IAT in mothers of DAT-positive babies. METHODS: DAT was performed with forward blood grouping on cord blood in term babies who were born between September 2020 and September 2022. IAT was performed in the mothers of the babies who were found to have a positive DAT and antibody identification was performed in the mothers who were found to have a positive IAT. Specific antibodies detected and identified were associated with the clinical course. RESULTS: The study included 2769 babies and their mothers. The prevalence of DAT positivity was found to be 3.3% (87 of 2661). In DAT-positive babies, the rate of ABO incompatibility was 45.9%, the rate of RhD incompatibility was 5.7% and the rate of RhD and ABO incompatibility in association was 10.3%. The rate of subgroup incompatibility and other red blood cell antibodies was 18.3%. Phototherapy was applied because of indirect hyperbilirubinemia in 16.6% of the DAT-negative babies and in 51.5% of the DAT-positive babies. The need for phototherapy was significantly higher in DAT-positive infants (p < 0.01). Severe hemolytic disease of the newborn, bilirubin level, duration of phototherapy and use of intravenous immunoglobulin were found to be significantly higher in the babies whose mothers were IAT positive compared with the babies whose mothers were IAT negative (p < 0.01). CONCLUSIONS: IAT should be performed on all pregnant women. When screening with IAT is not performed during pregnancy, performing DAT in the baby plays a key role. We showed that the clinical course was more severe when mothers of DAT-positive babies were IAT positive.

Significance of immunohematologic testing in mother and newborn ABO incompatibility.

The aim of this study was to define risk factors for jaundice and anemia in newborns with a positive direct antiglobulin test (DAT) and/or with an incompatible crossmatch due to ABO incompatibility between mother and newborn. ABO incompatibility has become a more significant cause of hemolytic disease of the fetus and newborn since the introduction of effective anti-D prophylaxis. The condition is common and, if clinically significant at all, causes only mild jaundice, which can be treated with phototherapy (PT). However, rare and serious presentations, requiring transfusion therapy, have been noted. Clinical, laboratory, and immunohematologic data were collected retrospectively from medical records of ABO-incompatible newborns and their mothers over a 5-year period (2016-2020) from University Hospital Centre Zagreb. Two groups of newborns were compared: those who needed medical intervention because of hyperbilirubinemia or anemia and those who did not. Within the group of newborns requiring intervention, we also compared those with A and B blood groups. Over the 5-year period, 72 of 184 (39%) newborns required treatment. The treatment was PT in 71 (38%) newborns and erythrocyte transfusion in 2 (1%). In 112 (61%) newborns, ABO incompatibility was an accidental finding while performing blood group typing; these newborns did not require any therapy. In conclusion, we found a statistical, but not clinically significant, difference between the groups of treated and untreated newborns, related to the mode of delivery and DAT positivity within hours of delivery. There were no statistically significant differences in characteristics between the groups of treated newborns, except for two newborns with blood group A who received erythrocyte transfusions.

Rates of phototherapy among ABO-incompatible newborns with a negative direct antiglobulin test.

OBJECTIVE: We analyze phototherapy rates after implementation of a Hyperbilirubinemia Clinical Pathway (HCP), which placed full-term ABOi DAT negative newborns on the low risk phototherapy nomogram, rather than medium risk, as previously done. STUDY DESIGN: A chart review was performed for ABOi newborns born ≥36 weeks gestation between January 2020 and October 2021. Primary outcome measures were rates of phototherapy across pre- and post-intervention groups and among DAT negative newborns. RESULTS: There was an increased proportion of newborns assigned to the low risk curve after the intervention. There were no significant differences in phototherapy rates among the intervention groups, although there was a non-significant decrease in phototherapy rates among DAT negative newborns after the intervention. There were no increases in adverse outcomes. CONCLUSIONS: Providers adhered to the guidelines after implementation of the HCP. ABOi DAT negative newborns can be viewed as low risk for hyperbilirubinemia requiring phototherapy.

The spectrum of ABO haemolytic disease of the fetus and newborn in neonates born to group O mothers.

BACKGROUND AND OBJECTIVES: ABO haemolytic disease of the fetus and newborn (HDFN) is a lesser recognized entity; however, the severity may vary in neonates. This prospective observational study was performed to determine the severity and risk of ABO-HDFN in neonates born to O group mothers. MATERIALS AND METHODS: A total of 260 neonates born to non-alloimmunized blood group O mothers were recruited. Blood group O neonates were excluded from the study. Neonatal direct antiglobulin test (DAT) was performed using the column agglutination technique. They were monitored for clinical and laboratory parameters and followed up at 6-8 weeks. The maternal anti-A and anti-B titres (IgM and IgG) were also done. RESULTS: A total of 176 neonates with blood group A (77/260; 29.6%) and B (99/260; 38.1%) were finally included in the study, and 15 (8.5%) of them were DAT positive. Overall, 26.7% (47/176) neonates received phototherapy, 172 (97.7%) survived and none required readmission. The median (inter-quartile range [IQR]) maternal IgG anti-B titre (32 [32-64]) was significantly higher (p < 0.001) than the IgG anti-A titre (16 [8-64]). The maximum total serum bilirubin in neonates had a significant positive association with neonatal birth weight (p = 0.045), positive DAT (p = 0.006) and requirement of phototherapy (p < 0.001). The relative risk (95% CI) of a DAT-positive neonate requiring phototherapy was 4.55 (3.12-6.33). CONCLUSION: The frequency of ABO incompatibility in neonates born to group O mothers was 67.69% (176/260). The maternal IgG titre of ≥64 could be a good predictor for identifying the neonates at risk of developing hyperbilirubinaemia requiring phototherapy.

International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn.

Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.

Retrospective analysis of direct antiglobulin test positivity at tertiary academic hospital over 10 years.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a clinically significant problem that may potentially affect any pregnancy. Direct antiglobulin test (DAT) is considered to be an important test in identifying newborns who are suspected to have HDN. This study aims in reviewing data regarding a positive DAT result concerning etiology and the development of HDN over a period of 10 years. STUDY DESIGN AND METHODS: A retrospective study of all neonates with a positive DAT result between January 2011 and December 2020 was performed. Data were obtained from patients' electronic hospital files, transfusion medicine databases, and medical birth records. Laboratory parameters along with clinical interventions in neonates with a DAT-positive result and a comparison group of DAT-negative neonates were performed. RESULTS: 36,000 deliveries were registered in this period. 176 (2.65 %) neonates had a positive DAT result. ABO-incompatibility was the most common cause with 59.1 %; Rh incompatibility 13.8 %, minor blood group incompatibility, and other RBC-related antibodies 10.1 %, and unspecified etiology in 17 % of cases. Among DAT-positive cases, 32.7 % of neonates were diagnosed with HDN. ABO-incompatibility was the major reason as well. Initial mean total bilirubin levels were higher in the DAT-positive group than the control group (p < 0.001), and these neonates also had a lower initial hemoglobin level (p < 0.001). The need for therapeutic interventions was significantly higher in DAT-positive neonates (p < 0.001) as 86.8 % underwent phototherapy, with 32.7 %, and 17.6 % receiving exchange transfusion (ET) and intravenous immunoglobulin (IVIG), respectively. CONCLUSION: In conclusion, ABO incompatibility was the most common cause for neonatal DAT positivity. Besides the common causes of DAT positivity, there would be rare but important conditions that may lead to a positive result, such as antibodies passively acquired from mothers in the context of alloimmunizations or using drugs. In addition, as a high rate of therapeutic intervention was identified among neonates with a DAT-positive result, there is a crucial need for increasing awareness regarding early diagnosis of the condition, careful monitoring, and the employment of prenatal alloimmunization screening tests.

Successful treatment of refractory pure red cell aplasia with eltrombopag after ABO-incompatible allogeneic hematopoietic stem cell transplantation.

Pure red cell aplasia (PRCA) is a well-recognized complication of ABO major mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a reported incidence of 10%-20% (Zhidong et al., 2012; Busca et al., 2018). It is clinically characterized by anemia, reticulocytopenia, and the absence of erythroblasts in a normal-appearing bone marrow biopsy (Shahan and Hildebrandt, 2015). The mechanism for PRCA has been presumed to be persistence of recipient isoagglutinins, produced by residual host B lymphocytes or plasma cells, which can interfere with the engraftment of donor erythroid cells (Zhidong et al., 2012). Several risk factors of PRCA at presentation are known, such as presence of anti-A isoagglutinins before transplantation, reduced intensity conditioning, absence of acute graft-versus-host disease (GVHD), sibling donors, and cyclosporin A (CsA) as GVHD prophylaxis (Hirokawa et al., 2013). PRCA is not considered to be a barrier to HSCT, as some patients can recover spontaneously or benefit from various approaches including high-dose steroids, erythropoietin (EPO), plasma exchange, immunoadsorption, donor lymphocyte infusion (DLI), treatment with rituximab, bortezomib, or daratumumab, and tapering or discontinuation of immunosuppression (Hirokawa et al., 2013; Bathini et al., 2019). However, there are still some patients who fail to respond even to aggressive treatment; they become red cell transfusion-dependent and iron-overloaded, and their life quality is impaired.

Acute hemolytic transfusion reaction caused by anti-Yta.

Many patients with anti-Yta receive multiple transfusions of Yt(a+) red blood cells (RBCs) with no ill effects. However, anti-Yta has been implicated in hemolytic transfusion reactions. Antibody identification typically determines specificity of antibodies and their clinical significance to justify blood requirements for antigen-negative blood when clinically significant antibodies are involved. Occasionally, specificity of antibody is of variable significance. Variability in clinical significance is a characteristic of anti-Yta that may affect the clinical management of such patients. This case reports the outcome of an incompatible transfusion in an 83-year-old female patient with anti-Yta, -D, -C, -Leab, and -HI who was admitted to the hospital for a severe urinary tract hemorrhage and fever. The patient was transfused with 1 crossmatch-incompatible group A, Yt(a+), D-, C-, E-, S- RBC unit in an emergency medical event. During that time, the patient exhibited chills, shivering, and tachycardia. Decreases in hemoglobin and hematocrit were noted. Laboratory parameters for hemolysis, such as total bilirubin, direct bilirubin, and lactate dehydrogenase, were increased. Based on clinical and laboratory evaluation, it was concluded that the patient had an acute hemolytic transfusion reaction caused by anti-Yta. The patient was successfully treated with antipyretics, antihistamines, and corticosteroids. Urinary tract hemorrhaging was stopped. Anemia was additionally improved with parenteral iron supplementation, and further transfusion was not required. Immunohematology 2021;37:13-17.Many patients with anti-Yta receive multiple transfusions of Yt(a+) red blood cells (RBCs) with no ill effects. However, anti-Yta has been implicated in hemolytic transfusion reactions. Antibody identification typically determines specificity of antibodies and their clinical significance to justify blood requirements for antigen-negative blood when clinically significant antibodies are involved. Occasionally, specificity of antibody is of variable significance. Variability in clinical significance is a characteristic of anti-Yta that may affect the clinical management of such patients. This case reports the outcome of an incompatible transfusion in an 83-year-old female patient with anti-Yta, -D, -C, -Leab, and -HI who was admitted to the hospital for a severe urinary tract hemorrhage and fever. The patient was transfused with 1 crossmatch-incompatible group A, Yt(a+), D­, C­, E­, S­ RBC unit in an emergency medical event. During that time, the patient exhibited chills, shivering, and tachycardia. Decreases in hemoglobin and hematocrit were noted. Laboratory parameters for hemolysis, such as total bilirubin, direct bilirubin, and lactate dehydrogenase, were increased. Based on clinical and laboratory evaluation, it was concluded that the patient had an acute hemolytic transfusion reaction caused by anti-Yta. The patient was successfully treated with antipyretics, antihistamines, and corticosteroids. Urinary tract hemorrhaging was stopped. Anemia was additionally improved with parenteral iron supplementation, and further transfusion was not required. Immunohematology 2021;37:13­17.

Prediction of ABO hemolytic disease of the newborn using pre- and perinatal quantification of maternal anti-A/anti-B IgG titer.

BACKGROUND: Hemolysis in fetus/newborns is often caused by maternal antibodies. There are currently no established screening procedures for maternal ABO antibodies harmful to fetus/newborn. We investigated the clinical significance, and predictive value of maternal anti-A/B titer for hyperbilirubinemia in ABO-incompatible newborns. METHODS: We conducted a case-control study of blood group O mothers and their ABO-compatible (O) vs. -incompatible (A/B) newborns receiving phototherapy, and of ABO-incompatible newborns receiving phototherapy vs. no phototherapy. Newborn data and treatment modalities were recorded, and total serum bilirubin and hemoglobin were measured. Maternal anti-A/B immunoglobulin-γ (IgG) titers were measured prenatally and perinatally, and negative and positive predictive values (NPV, PPV) were calculated to assess the risk of developing hyperbilirubinemia requiring phototherapy. RESULTS: We found a significantly higher maternal IgG antibody titer in the case group (p < 0.001). Maternal anti-A/B titers at first trimester had modest predictive values: NPV = 0.82 and PPV = 0.65 for neonatal hyperbilirubinemia; titers at birth improved the predictive values: NPV = 0.93 and PPV = 0.73. Newborn hemoglobin was significantly lower in incompatibles compared to compatibles (p = 0.034). Furthermore, increased anti-A/B IgG production during pregnancy was associated with hyperbilirubinemia and hemolysis in incompatible newborns. CONCLUSIONS: There was a significant association between maternal anti-A/B IgG titer and hyperbilirubinemia requiring treatment. IMPACT: Maternal anti-A/B IgG titer in the first trimester and at birth is predictive of hemolytic disease of the ABO-incompatible newborn. Increased IgG anti-A/B production throughout pregnancy in mothers to ABO-incompatible newborns developing hyperbilirubinemia contrasts a constant or reduced production in mothers to newborns not developing hyperbilirubinemia. Screening tools available in most immunohematology laboratories can identify clinically important IgG anti-A/B. Use of maternal samples taken at birth yielded NPV = 0.93 and PPV = 0.73.

Hemolytic anemia caused by non-D minor blood incompatibilities in a newborn.

Hyperbilirubinemia is one of the most widely seen cause of neonatal morbidity. Besides ABO and Rh isoimmunization, minor blood incompatibilities have been also been identified as the other causes of severe newborn jaundice. We report a newborn with indirect hyperbilirubinemia caused by minor blood group incompatibilities (P1, M, N, s and Duffy) whose hemolysis was successfully managed with intravenous immunoglobulin therapy. A thirty-two gestational weeks of preterm male baby became severely icteric on postnatal day 11, with a total bilirubin level of 14.66 mg/dl. Antibody screening tests revealed incompatibility on different minor groups (P1, M, N, s and Duffy (Fya ve Fyb)). On postnatal day thirteen, the level of bilirubin increased to 20.66 mg/dl although baby was under intensive phototherapy. After the administration of intravenous immunoglobulin and red blood cell transfusion, hemoglobin and total bilirubin levels became stabilised. Minor blood incompatibilities should be kept in mind during differential diagnosis of hemolytic anemia of the newborn. They share the same treatment algorithm with the other types hemolytic anemia. New studies revealed that intravenous immunoglobulin treatment in hemolytic anemia have some attractive and glamorous results. It should be seriously taken into consideration for treatment of minor blood incompatibilities.

Anemic Disease of the Newborn With Little Increase in Hemolysis and Erythropoiesis Due to Maternal Anti-Jra: A Case Study and Review of the Literature.

The severity of the hemolytic disease of the fetus and newborn (HDFN) due to Jra mismatch ranges from no symptoms to severe anemia that requires intrauterine and exchange transfusions. We encountered a newborn, born to a healthy mother having anti-Jra at 38 weeks of pregnancy, who had moderate anemia, a positive direct antiglobulin test (DAT) result, no increased erythropoiesis, and no jaundice at birth. Flow cytometry revealed that the Jra antigen of red cells in the infant was nearly negative at birth, biphasic at 5 weeks, and lowly expressed at 7 months of life. We searched online for previous case reports on HDFN due to Jra incompatibility. Among 63 reported cases, excluding 25 cases, 38 were included with the present case for analysis. Of 39 newborns, 10 developed clear anemia (hemoglobin <10.0 g/dL), and 1 died, 5 developed hydrops fetalis, 4 needed intrauterine transfusion and/or exchange transfusion, and 3 received red cell transfusion after birth; overlaps were included. Among 29 neonates with no anemia, 8 needed interventions including phototherapy and γ-globulin infusion, and the remaining 21 received conservative supports only. The maternal anti-Jra titer, ranging between 4 and 2048, did not correlate with the severity of anemia, levels of bilirubin, or any interventions required. The DAT of red cells was positive in 29 of 36 fetuses/newborns tested, whereas it was often negative among anemic neonates (4 of 9) (P < .05). Hematopoiesis did not increase effectively, as indicated by reticulocyte ratios between 1.7% and 22.3%, even with the increase in reticulocytes in anemic neonates compared with nonanemic neonates (P < .05). Total bilirubin levels ranged broadly between 0.2 and 14.3 mg/dL but were generally low. The maternal anti-Jra titer and IgG3 subclass did not correlate with the morbidity of the newborns. Being identical/compatible between mothers and their infants may possibly enhance infants' morbidity, as a weak tendency was observed (P = .053). Maternal anti-Jra may suppress erythropoiesis in fetuses via a mechanism different from the established HDFN, such as anti-D, as evidenced by the lower reticulocyte count and small increase in bilirubin in neonates. As the anti-Jra titer, IgG subclass, and DAT were not correlated with the severity, the mechanism of anti-Jra-induced HDFN remains to be elucidated.

Unusual cause of severe neonatal hyperbilirubinaemia: a twin case.

We present twins born to the 31-year-old, multigravida mother, who were referred to our centre at 90 hours of life for severe hyperbilirubinaemia. Twin 1 had already received two double volume exchange transfusions at 55 and 83 hours of life, in view of the persistent rise in bilirubin despite receiving phototherapy. Twin 2 had received phototherapy and 1 packed red blood cell transfusion in view of the fall in haematocrit. Mother's blood group was B positive and that of both twins was O positive. Both the twins were started on intensive phototherapy and their serum bilirubin and haematocrit were evaluated. On investigation, a minor blood incompatibility was found. Double volume exchange transfusion was done for twin 2 at 100 hours of life in view of the rapid rise in serum bilirubin. Both the babies were monitored for their serum bilirubin and treated for sepsis and discharged after 15 days.

Retrospective analysis of HDFN due to ABO incompatibility in a single institution over 6 years.

OBJECTIVES: To study the rate of ABO haemolytic anaemia of fetus and newborn (HDFN) in one institution over 6 years. BACKGROUND: ABO major incompatibility between mothers and their newborns occurs in about 10% of births. So, mothers with an O blood group may form IgG-class antibodies against A and B antigens, which could pass across the placenta and lead to a variable degree of HDFN in the newborn. METHODS: At our institution, we have reviewed data regarding ABO-based HDFN in the last 6 years. RESULTS: We found that, in 28 089 deliveries, an ABO major incompatibility between mothers and newborns occurs in 11% of cases, with 72% of O/A and 28% of O/B incompatibility. In turn, 23% of these newborns had an eluate-confirmed positive direct antiglobulin test [DAT; 74% (511) were due to anti-A and 26% (179) to anti-B], with 1·0% requiring invasive treatments (exchange transfusion or intravenous immunoglobulin). Overall, 2·5% of the total newborns had a positive DAT for an anti-A or anti-B antibody, and 0·11% required invasive treatment in addition to phototherapy for their HDFN. CONCLUSIONS: Serological ABO HDFN is a relatively frequent event when an O-A/O-B incompatibility between mothers and their newborn occurs and, in most cases, translates into a self-limiting disease, with a small number of newborns requiring invasive treatments. The DAT test, although not predictive of disease severity, appears to be a useful tool to monitor babies born from O-A/O-B-incompatible pregnancies and to identify those who may require treatment.

Is Cord Blood Bilirubin Level a Reliable Predictor for Developing Significant Hyperbilirubinemia?

OBJECTIVE: We aimed to investigate whether cord blood bilirubin (CBB) level could be used to identify the newborns at a high risk of developing hyperbilirubinemia. STUDY DESIGN: Total and direct serum bilirubin level were evaluated from umbilical cord blood of newborns. We checked blood groups and Rh status of all mothers and determined blood groups and direct Coombs test (DC) of newborns born to mothers whose blood group was O type or Rh negative to determine the maternal-fetal blood group or Rh incompatibility. RESULTS: A total of 418 newborns were included, and phototherapy (PT) was required in 17 newborns. The cutoff value of CBB for predicting the occurrence of significant hyperbilirubinemia requiring PT was 1.67 mg/dL, with a sensitivity of 82% and specificity of 99%. The mean CBB level in babies receiving PT was 2.4 ± 0.9 mg/dL. When blood group, CBB level, DC, gender, and mode of delivery were assigned as possible risk factors, multivariate analysis showed ABO, Rh incompatibility, and CBB level increased the risk of PT requirement. CONCLUSION: CBB could be useful to determine newborns at a risk of developing hyperbilirubinemia and prevent developing severe complications due to delay in diagnosis.

Severe ABO Hemolytic Disease of the Newborn Requiring Exchange Transfusion.

ABO incompatibility (ABOi), the most common cause of hemolytic disease of the newborn (HDN), is nearly always mild and treatable with phototherapy. Reports of ABOi HDN requiring neonatal exchange transfusion are extremely rare since the inception of modern guidelines. Here, a case of ABOi HDN clearly met criteria for exchange transfusion. An O-positive African American mother delivered a B-positive neonate that quickly developed hyperbilirubinemia. The neonatal DAT was positive from anti-B and anti-A,B, and maternal IgG titer was 1024. Double volume exchange transfusion resulted in a favorable outcome. Given early discharge of newborns, further understanding of factors predicting severe disease is needed.

Indirect neonatal hyperbilirubinemia in hospitalized neonates on the Thai-Myanmar border: a review of neonatal medical records from 2009 to 2014.

BACKGROUND: Indirect neonatal hyperbilirubinemia (INH) is a common neonatal disorder worldwide which can remain benign if prompt management is available. However there is a higher morbidity and mortality risk in settings with limited access to diagnosis and care. The manuscript describes the characteristics of neonates with INH, the burden of severe INH and identifies factors associated with severity in a resource-constrained setting. METHODS: We conducted a retrospective evaluation of anonymized records of neonates hospitalized on the Thai-Myanmar border. INH was defined according to the National Institute for Health and Care Excellence guidelines as 'moderate' if at least one serum bilirubin (SBR) value exceeded the phototherapy threshold and as 'severe' if above the exchange transfusion threshold. RESULTS: Out of 2980 records reviewed, 1580 (53%) had INH within the first 14 days of life. INH was moderate in 87% (1368/1580) and severe in 13% (212/1580). From 2009 to 2011, the proportion of severe INH decreased from 37 to 15% and the mortality dropped from 10% (8/82) to 2% (7/449) coinciding with the implementation of standardized guidelines and light-emitting diode (LED) phototherapy. Severe INH was associated with: prematurity (< 32 weeks, Adjusted Odds Ratio (AOR) 3.3; 95% CI 1.6-6.6 and 32 to 37 weeks, AOR 2.2; 95% CI 1.6-3.1), Glucose-6-phosphate dehydrogenase deficiency (G6PD) (AOR 2.3; 95% CI 1.6-3.3), potential ABO incompatibility (AOR 1.5; 95% CI 1.0-2.2) and late presentation (AOR 1.8; 95% CI 1.3-2.6). The risk of developing severe INH and INH-related mortality significantly increased with each additional risk factor. CONCLUSION: INH is an important cause of neonatal hospitalization on the Thai-Myanmar border. Risk factors for severity were similar to previous reports from Asia. Implementing standardized guidelines and appropriate treatment was successful in reducing mortality and severity. Accessing to basic neonatal care including SBR testing, LED phototherapy and G6PD screening can contribute to improve neonatal outcomes.

Red blood cell alloimmunization in pregnancy during the years 1996-2015 in Iceland: a nation-wide population study.

BACKGROUND: Red blood cell (RBC) alloimmunization during pregnancy is still a major problem. Historically, anti-D antibodies are most likely to cause severe hemolysis, but other antibodies are also important. In Iceland, postnatal RhIg prophylaxis was implemented in 1969, universal RBC antibody screening was implemented in 1978, but antenatal RhIg prophylaxis is not yet routine. STUDY DESIGN AND METHODS: This nation-wide population study gathered data on alloimmunized pregnancies in Iceland between 1996 and 2015. Blood bank alloimmunization data were linked to Icelandic Medical Birth Registry data. RBC antibodies were classified as either clinically significant or clinically nonsignificant. RESULTS: In total, 912 positive antibody screens from 87,437 births were identified (1.04% prevalence). The most frequent antibodies were anti-M (19.4%), anti-E (19.0%), and anti-D (12.5%). Anti-D prevalence among D-negative mothers was 1.1%. Icelandic Medical Birth Registry data were available for 881 (96.6%) pregnancies. In the clinically significant group (n = 474), anti-E (27%) and anti-D (20%) were most common, whereas anti-M was most frequent (53%) in the clinically nonsignificant group (n = 407). Mothers in the clinically significant group were older, more often multigravidae, had more abortions and stillbirths, and had shorter gestational length. Newborns in the clinically significant group were less healthy, had lower weight and Apgar scores, and required more treatment. Among specificities in the clinically significant group, anti-D antibodies were most strongly associated with severe hemolysis. CONCLUSION: In this study, the prevalence of alloimmunization was similar to that in previous reports. Of all clinically significant antibodies, anti-D was most strongly associated with severe hemolysis, requiring phototherapy or exchange transfusions. Our data emphasize the importance of implementing an antenatal prophylactic RhIg program in Iceland in the near future.

Oral administration of Chinese herbal medicine during gestation period for preventing hemolytic disease of the newborn due to ABO incompatibility: A systematic review of randomized controlled trials.

BACKGROUND: About 85.3% of hemolytic disease of the newborn (HDN) is caused by maternal-fetal ABO blood group incompatibility. However, there is currently no recommended "best" therapy for ABO incompatibility during pregnancy. OBJECTIVES: To systematically assess the safety and effectiveness of oral Chinese herbal medicine (CHM) for preventing HDN due to ABO incompatibility. METHODS: The protocol of this review was registered on the PROSPERO website (No. CRD42016038637).Six databases were searched from inception to April 2016. Randomized controlled trials (RCTs) of CHM for maternal-fetal ABO incompatibility were included. The primary outcome was incidence of HDN. The Cochrane risk of bias tool was used to assess the methodological quality of included trials. Risk ratios (RR) and mean differences with 95% confidence interval were used as effect measures. Meta-analyses using Revman 5.3 software were conducted if there were sufficient trials without obvious clinical or statistical heterogeneity available. RESULTS: Totally 28 RCTs involving3413 women were included in the review. The majority of the trials had unclear or high risk of bias. Our study found that the rate of HDN and the incidence of neonatal jaundice might be 70% lower in the herbal medicine group compared with the usual care group (RR from 0.25 to 0.30).After treatment with herbal medicine, women were twice as likely to have antibody titers lower than 1:64 compared with women who received usual care(RR from 2.15 to 3.14) and the umbilical cord blood bilirubin level in the herbal medicine group was 4umol/L lower than in those receiving usual care. There was no difference in Apgar scores or birthweights between the two groups. CONCLUSIONS: This review found very low-quality evidence that CHM prevented HDN caused by maternal-fetal ABO incompatibility. No firm conclusions can be drawn regarding the effectiveness or safety of CHM for this condition.