Neonatal and Obstetrical Outcomes of Pregnancies Complicated by Alloimmunization.

BACKGROUND AND OBJECTIVES: Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in ∼4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors. METHODS: We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes. RESULTS: A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion. CONCLUSIONS: Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia.

Maternal red blood cell alloimmunization prevalence in the United States.

ABSTRACT: Hemolytic disease of fetus and newborn (HDFN) is a life-threatening disease mediated by maternal alloimmunization to red blood cell (RBC) antigens. Studies of maternal alloimmunization prevalence in the United States lack national data. This study describes prevalence and trends in alloimmunization in pregnancy in the United States. RBC antibodies (abs) were identified in a large, nationwide, commercial laboratory database from 2010 through 2021. The cohort comprised pregnancies for which the year of laboratory collection and patient's state of residence were available. Data were normalized based on US Centers for Disease Control and Prevention estimates of live births and weighted by year and US Census Division. Cochrane-Armitage tests assessed temporal trends of alloimmunization. Of 9 876 196 pregnancies, 147 262 (1.5%) screened positive for RBC abs, corresponding to an estimated prevalence of 1518 of 100 000 pregnancies. Of identified RBC abs, anti-D comprised 64.1% pregnancies (586/100 000). Prevalence of other high-risk RBC abs for HDFN included anti-K (68/100 000) and anti-c (29/100 000). Incidence of all 3 high-risk abs increased from 2010 to 2021 (all P < .001). Among almost 10 million pregnancies in the United States, comprising an estimated 14.4% of all pregnancies, 1.5% screened positive for RBC abs. Almost three-quarters (679/100 000 [74.3%]) of RBC abs identified were high risk for HDFN. Although prevalence of anti-D is difficult to interpret without the ability to distinguish alloimmunization from passive immunity, it remains problematic in HDFN, ranking second only to anti-K in critical titers. Given the sequelae of HDFN, new initiatives are required to reduce the incidence of alloimmunization in patients of reproductive potential.

Neurosonographic Findings in Infants with Rhesus Hemolytic Disease of Newborn: A Prospective Observational Study.

We estimated the incidence of intraventricular hemorrhage (IVH) and/or periventricular leukomalacia/echogenicity (PVL/E) in Rhesus isoimmunized infants. Seventy-one infants underwent cranial ultrasound within the first 3 days of life or discharge, whichever was earlier. Of these, 27 (38%) infants had IVH/ PVL/E. On multivariate analysis, lower gestational age (P = 0.035), small for gestational age [aOR (95% CI) 10.6 (1.9, 58.9)], and sepsis [aOR (95% CI) 4.5 (1.1, 18.4)] were independently associated with IVH/PVL.

An ongoing problem: Rhesus hemolytic disease of the newborn - A decade of experience in a single centre.

BACKGROUND: The objectives were to evaluate the descriptive features of newborns with a diagnosis of Rhesus (Rh) hemolytic disease, to determine the morbidity and mortality rates, to evaluate the treatment methods and the factors affecting treatment requirements and clinical outcomes during a ten-year period at a tertiary center. METHODS: Newborn infants who had a positive direct Coombs test and/or had a history of intrauterine transfusion (IUT) due to Rh hemolytic disease were included. The data regarding the prenatal, natal and postnatal periods were collected from hospital records. RESULTS: A total of 260 neonates were included of which 51.2% were female. The mean ± standard deviation gestational age was 36.9 ± 2.7 weeks. The rate of preterm birth was 41.2%. Of 257 mothers whose obstetric medical history could be accessed, 87.2% were multigravida, whereas 76.3% were multiparous. Among mothers who had a reliable history of anti-D immunoglobulin prophylaxis (n=191), 51.3% had not received anti-D immunoglobulin prophylaxis in their previous pregnancies. The antenatal transfusion rate was 31.7% and the frequency of hydrops fetalis was 8.8%. While combined exchange transfusion (ET) and phototherapy (PT) was performed in 15.4% of the babies, the majority either needed phototherapy only (51.1%) or no treatment (33.5%). The mortality rate was 3.8 % (n = 10), and nine babies out of these 10 were those with severe hydrops fetalis. CONCLUSION: This study showed that Rh hemolytic disease is still a major problem in developing countries. Multiple comorbidities may occur in addition to life threatening complications, including hydrops fetalis, anemia and severe hyperbilirubinemia. High rates of multiparity and low rates of anti-D immunoglobulin prophylaxis are potential barriers for the eradication of the disease. It should be remembered that Rh hemolytic disease is a preventable disease in the presence of appropriate antenatal follow-up and care facilities.

Severity of haemolytic disease of the fetus and newborn in patients with a history of intrauterine transfusions in a previous pregnancy: A nationwide retrospective cohort study.

OBJECTIVE: Pregnant women who received at least one intrauterine transfusion (IUT) for haemolytic disease of the fetus and newborn (HDFN) in the preceding pregnancy are presumed to have a high likelihood of requiring IUTs again, often starting at an earlier gestational age. Our aim was to quantify these risks in a large national cohort. DESIGN: Retrospective cohort study of a nationwide Dutch database. SETTING: The Netherlands. POPULATION: All women treated in The Netherlands with IUTs for Rhesus D (RhD)- or Kell-mediated HDFN between 1999 and 2017 and their follow-up pregnancies were included. Pregnancies with an antigen-negative fetus were excluded. METHODS: Electronic patient files were searched for the number and gestational age of each IUT, and analysed using descriptive statistics and linear regression. MAIN OUTCOME MEASURES: Percentage of women requiring one or more IUTs again in the subsequent pregnancy, and gestational age at first IUT in both pregnancies. RESULTS: Of the 321 women in our study population, 21% (69) had a subsequent ongoing pregnancy at risk. IUTs were administered in 86% (59/69) of cases. In subsequent pregnancies, the median gestational age at first IUT was 3 weeks earlier (interquartile range -6.8 to 0.4) than in the preceding pregnancy. CONCLUSIONS: Our study shows that pregnant women with a history of IUTs in the previous pregnancy are highly likely to require IUTs again, and on average 3 weeks earlier. Clinicians need to be aware of these risks and ensure timely referral, and close surveillance from early pregnancy onwards. Additionally, for women with a history of IUT and their caregivers, this information is essential to enable adequate preconception counselling.

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.

A study on diagnostic performance of different immunohematological diagnostic tests in assessing the prevalence of ABO Hemolytic Disease of Newborn in the antenatal O group mothers and their neonatal outcome in a tertiary care hospital in Northern India.

BACKGROUND: Hemolytic disease of the newborn (HDN) results in the decreased lifespan of the red cells. HDN related to ABO incompatibility is mostly unnoticed because routine screening is not being done. This study was done to assess the prevalence of ABO-HDN and to compare different immunohematological tests. Methods-In this study 213 O group mothers and the 122 ABO-incompatible newborns born to them were included. Quantifying the maternal IgG anti-A/anti-B antibody titer was done by Conventional Tube Technique (CTT) using Dithiothreitol (DTT) pretreated maternal serum. Hemolysin test was performed on the mothers having titer > 256. These cases were followed up and, after delivery, were monitored for ABO HDN, along with direct antiglobulin testing and elution studies. The prevalence of ABO-HDN was calculated, and the different diagnostic parameters of the tests were calculated. Results- The prevalence of ABO-HDN in our population was estimated to be 1.7%, 6.1% & 10.6% in our population, O group mothers, and O group mothers with ABOincompatible newborns, respectively. Maternal titer≥ 512 strongly correlated with ABOHDN. DAT positivity is a good predictor of ABO-HDN, especially using sensitive techniques. Maternal IgG titers have the highest sensitivity & Negative Predictive Value, while DAT has the highest specificity & Positive Predictive Value. Conclusion - Maternal ABO antibody titration may be advocated in the centers to identify high-risk groups. It can advocate institutional delivery and dedicated follow-up of newborns with ABO-HDN. Blood grouping & DAT may be performed in all newborns born to O blood group to identify high-risk cases.

Immunoglobulin for hemolytic jaundice in Japan: A retrospective survey.

BACKGROUND: Intravenous immunoglobulin G (IVIG) is used to treat blood-type incompatibility hemolytic disease of newborns (BTHDN). Although IVIG's efficacy for treating BTHDN has been challenged, as an updated systematic review suggests, IVIG could significantly reduce exchange transfusions. We conducted a mail-in questionnaire survey to ascertain actual use of IVIG for BTHDN in Japan. METHODS: The survey, conducted in 2014, included infants born between January 1, 2009, and December 31, 2013. Questionnaires were sent to the heads of neonatal intensive care units (NICUs) at perinatal centers of the Japan Neonatologist Association. RESULTS: A total of 195 centers (64.6%) responded to the questionnaire. During the study period, 170 centers (87.2%) reported incidences of BTHDN. Among these centers, there were 1726 diagnosed cases of BTHDN in neonates. Of these cases, 419 infants were treated with IVIG in 127 centers, representing approximately 74.7% of all centers. After the exclusion of cases with missing data and those where consent for data usage was not obtained, a total 916 infants were included in this study. Of these, 219 (23.9%) were treated with IVIG after phototherapy, and 187 (20.4%) of these infants did not require further blood exchange transfusion. The IVIG dosages ranged from 40 to 1200 mg/kg/dose, but the majority were between 500 and 1000 mg/kg/dose, with a median of 800 mg/kg/dose. About 20% of the infants treated with IVIG showed late-onset anemia and required treatment. Adverse events were reported in less than 1% of infants. CONCLUSIONS: For the treatment of BTHDN, IVIG administration was widely used in NICUs in Japan without severe adverse events.

Anti-C causing severe hemolytic disease of the fetus and newborn: a rare case report.

Hemolytic disease of the fetus and newborn (HDFN) due to anti-D was severe and fatal before the development of RhD immune prophylaxis. Proper screening and universal administration of Rh immune globulin has decreased the incidence of HDFN to a great extent. Pregnancy, transfusion, and transplantation still increase the chances of other alloantibody formation and the potential for HDFN. Advanced methods for immunohematology investigation allow for the identification of alloantibodies causative for HDFN other than anti-D. Many antibodies have been reported to cause HDFN, but there is scant literature where isolated anti-C is responsible for HDFN. We present here a case of severe HDFN caused by anti-C leading to severe hydrops and death of the neonate despite three intrauterine transfusions and other measures.

Hemolytic disease of the fetus and newborn: systematic literature review of the antenatal landscape.

BACKGROUND: Prevention of pregnancy-related alloimmunization and the management of hemolytic disease of the fetus and newborn (HDFN) has significantly improved over the past decades. Considering improvements in HDFN care, the objectives of this systematic literature review were to assess the prenatal treatment landscape and outcomes of Rh(D)- and K-mediated HDFN in mothers and fetuses, to identify the burden of disease, to identify evidence gaps in the literature, and to provide recommendations for future research. METHODS: We performed a systematic search on MEDLINE, EMBASE and clinicaltrials.gov. Observational studies, trials, modelling studies, systematic reviews of cohort studies, and case reports and series of women and/or their fetus with HDFN caused by Rhesus (Rh)D or Kell alloimmunization. Extracted data included prevalence; treatment patterns; clinical outcomes; treatment efficacy; and mortality. RESULTS: We identified 2,541 articles. After excluding 2,482 articles and adding 1 article from screening systematic reviews, 60 articles were selected. Most abstracted data were from case reports and case series. Prevalence was 0.047% and 0.006% for Rh(D)- and K-mediated HDFN, respectively. Most commonly reported antenatal treatment was intrauterine transfusion (IUT; median frequency [interquartile range]: 13.0% [7.2-66.0]). Average gestational age at first IUT ranged between 25 and 27 weeks. weeks. This timing is early and carries risks, which were observed in outcomes associated with IUTs. The rate of hydrops fetalis among pregnancies with Rh(D)-mediated HDFN treated with IUT was 14.8% (range, 0-50%) and 39.2% in K-mediated HDFN. Overall mean ± SD fetal mortality rate that was found to be 19.8%±29.4% across 19 studies. Mean gestational age at birth ranged between 34 and 36 weeks. CONCLUSION: These findings corroborate the rareness of HDFN and frequently needed intrauterine transfusion with inherent risks, and most births occur at a late preterm gestational age. We identified several evidence gaps providing opportunities for future studies.

Neonatal sepsis in alloimmune hemolytic disease of the fetus and newborn: A retrospective cohort study of 260 neonates.

BACKGROUND: Among neonates with hemolytic disease of the fetus and newborn (HDFN), we aimed to describe the frequency of central-line use, indications for insertion, and incidence of confirmed and suspected sepsis, including antibiotic treatment over a 10-year surveillance period. STUDY DESIGN AND METHODS: All neonates with HDFN admitted to our neonatal intensive care unit between January 2012 and December 2021 were included in this retrospective, cohort study. Annual proportions of infants with a central-line and central-line-associated bloodstream infection (CLABSI) rates (per 1000 central-line days and per 100 infants) were evaluated. Numbers of confirmed and suspected early- and late-onset sepsis episodes were assessed over the entire study period. RESULTS: Of the 260 included infants, 25 (9.6%) were evaluated for suspected sepsis, with 16 (6.2%) having ≥1 confirmed sepsis episode. A total of 123 central-lines were placed in 98 (37.7%) neonates, with impending exchange transfusion (ET) being the most frequent indication. Of the 34 (34.7%) neonates in whom a central-line was placed due to impending ET, 11 (32.4%) received no ET. Overall CLABSI incidence was 13.58 per 1000 central-line days. Neonates with a central-line had a higher risk for confirmed late-onset infection (RR 1.11, 95% CI: 1.04-1.20) and sepsis work-up (RR 1.10, 95% CI: 1.03-1.17) compared to infants without a central-line. CONCLUSIONS: Sepsis incidence among neonates with HDFN remains high, in particular in those with a central-line. Considering the substantial proportion of neonates with a central-line without eventual ET, central-line placement should be delayed until the likelihood of ET is high.

A cross-sectional study of haemolytic disease of the newborn in Uganda.

BACKGROUND AND OBJECTIVES: Haemolytic disease of the newborn (HDN) is an immune haemolytic anaemia from maternal alloantibodies. Rh immunoglobulin (RhIg) prophylaxis can prevent alloimmunization to the D antigen. However, RhIg is not universally available in Uganda. ABO incompatibility also causes HDN. We determined the prevalence of HDN among newborn infants with jaundice in Uganda. MATERIALS AND METHODS: We conducted a prospective cross-sectional study at Kawempe National Referral Hospital, Kampala, Uganda. Infants aged 0-14 days with neonatal jaundice (or total bilirubin >50 µmol/L) were enrolled. Clinical evaluation and laboratory testing, including ABO, RhD typing and maternal antibody screen, were performed. RESULTS: A total of 466 babies were enrolled. The mean (SD) age was 3.4 (1.5) days. Of newborn babies with jaundice, 17.2% (80/466) had HDN. Babies with HDN had lower haemoglobin (SD); 15.7 (2.7) compared with those without HDN; 16.4 (2.4) g/dL, p = 0.016; and a higher bilirubin (interquartile range); 241 (200-318) compared with those without HDN; 219 (191-263) µmol/L, p < 0.001. One baby had anti-D HDN, while 46/466 had HDN from an ABO incompatibility (anti-A 43.5% and anti-B 56.5%); 82% of babies with HDN also had suspected neonatal sepsis or birth asphyxia. About 79.2% (57/72) of mothers did not have ABO/Rh blood group performed antenatally. All infants with HDN survived except one. CONCLUSION: Among newborn infants with jaundice, HDN is not rare. The majority is due to ABO HDN affecting group A and group B babies equally. Ensuring routine ABO/Rh grouping for all pregnant women is an area for improvement.

Hemolytic disease of the fetus and newborn caused by anti-sD antibody in a GP.Mur/Mur Thai mother and review of the prevalence of sD in Thai blood donors.

BACKGROUND: Low-prevalence antigen sD (MNS23) is encoded by GYPB c.173C > G. Hemolytic disease of the fetus and newborn (HDFN) due to anti-sD is rare. A mother delivered a newborn whose red blood cells (RBCs) were DAT-positive and was later diagnosed with HDFN. Serum from the mother was incompatible with the father's RBCs and was used to screen 184 Thai blood donors. This study aimed to investigate the cause of HDFN in a Thai family and determine the prevalence of sD in Thai blood donors. MATERIALS AND METHODS: Three family members and four blood donors were investigated in the study. Massively Parallel Sequencing (MPS) was used for genotyping. Standard hemagglutination techniques were used in titration studies, phenotyping, and enzyme/chemical studies. Anti-s, anti-Mia , anti-JENU, and anti-sD reagents were used in serological investigations. RESULTS: The mother was GYP*Mur/Mur. The father and the four donors were GYPB*s/sD predicting S - s + sD +. The baby was GYP*Mur/sD and his RBCs were Mia +, s + w with anti-s (P3BER) and JENU+w . RBCs from two GYPB*sD -positive blood donors reacted with anti-sD (Dreyer). Proteolytic enzyme α-chymotrypsin-treated sD + cells did not react with anti-sD (Wat) produced by the GP.Mur/Mur mother but reacted with the original anti-sD (Dreyer). DISCUSSION: This is the first report of HDFN due to anti-sD in the Asian population. The genotype frequency for GYPB*sD in a selected Thai blood donor population is 2.2% (4/184). Anti-sD should be considered in mothers with Southeast Asian or East Asian background when antibody identification is unresolved in pregnancies affected by HDFN.

Population-based incidence and risk factors for cholestasis in hemolytic disease of the fetus and newborn.

OBJECTIVE: To estimate the incidence of cholestasis in neonates with hemolytic disease of the fetus and newborn (HDFN) and investigate risk factors and long-term liver disease. STUDY DESIGN: A population-based cohort study of all infants born with HDFN within the Stockholm region between 2006 and 2015. The study period was the first 90 days of life, and presence of any chronic liver disease was evaluated at two years of age. RESULTS: Cholestasis occurred in 7% (11/149). Median age at detection was 1.1 days. Intrauterine blood transfusions and maternal alloimmunization with multiple red blood cell antibodies including D-, c- or K-antibodies were independent risk factors for cholestasis. No infant had chronic liver disease at two years of age. CONCLUSIONS: Infants with severe HDFN have increased risk for cholestasis, particularly those requiring multiple intrauterine transfusions. Early and repeated screening for conjugated hyperbilirubinemia in the first week of life is needed to ensure adequate management.

Perinatal risk factors associated with severity of haemolytic disease of the foetus and newborn due to Rhc maternal-foetal incompatibility: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: Anti-c is the third red blood cell antibody responsible for haemolytic disease of the foetus and newborn (HDFN) requiring intrauterine transfusion. We aimed to identify risk factors associated with HDFN and severe HDFN due to Rhc maternal-foetal incompatibility. MATERIALS AND METHODS: A retrospective cohort study was conducted in Paris and the surrounding area (France), between 2013 and 2015. We included mothers and their children managed by the National Reference Centre in Perinatal Hemobiology for alloimmunization and maternal-foetal incompatibility for the Rhc antigen (N = 121). We conducted bivariate analyses to assess a relationship between perinatal factors (e.g., titre and concentration of anti-c antibodies, direct antiglobulin test) and HDFN, its severity and duration. RESULTS: The incidence of HDFN was 30% (n = 36), including 11% of severe HDFN (n = 13). Seven percent (n = 9) of neonates received at least one transfusion during the first week and 21% (n = 26) after this period until 3 weeks of life. During pregnancy, a concentration ≥7.5 IU/ml and a titre ≥4 and above were associated with HDFN and severe HDFN (p < 0.05). At birth, the high intensity of the quantitative direct antiglobulin test was associated with HDFN and severe HDFN (p < 0.05). A concentration ≥15 IU/ml is the best factor (area under curve [AUC] = 0.78) in predicting HDFN, followed by a titre ≥8 (AUC = 0.76). CONCLUSION: Anti-c alloimmunization causes neonatal anaemia, which is often belated. Paediatricians have to be aware of these risk factors and organize prolonged monitoring of neonates.

Exchange transfusions in severe Rh-mediated alloimmune haemolytic disease of the foetus and newborn: a 20-year overview on the incidence, associated risks and outcome.

BACKGROUND AND OBJECTIVES: Guidelines and indications for exchange transfusion in haemolytic disease of the foetus and newborn (HDFN) have changed drastically in the past decades, causing a decline in exchange transfusion rate. This study aims to evaluate the incidence of exchange transfusions (ETs) in neonates with Rh-mediated HDFN over the past 20 years at our centre, and report potentially ET-related complications as well as indicators for bilirubin encephalopathy. MATERIAL AND METHODS: In this observational study, 438 neonates were included with HDFN, born ≥ 35 weeks gestational age at the Leiden University Medical Centre between January 2000 and July 2020. The incidence of ET and procedure-related complications were assessed in three consecutive time periods determined by changes in guidelines and indications for ET. RESULTS: The incidence of ET in our centre declined from (104/156) 67% (time period 2000-2005), to (39/181) 22% (2006-2015) and to (10/101) 10% (2015-2020, p < 0·001). The maximum bilirubin levels in neonates after birth increased from 13·6 mg/dL (or 233 µmol/L), to 15·0 mg/dL (257 µmol/L) and to 15·3 mg/dL (263 µmol/L). The incidence of complications associated with the use of ET (including sepsis, haematologic disorders and respiratory failure) remained stable throughout the years, and no neonates died during the study period. CONCLUSION: Exchange transfusion incidence declined significantly over the past two decades. Decrease in ET incidence, and concomitant decrease in exposure and expertise, was not associated with an increase in procedure-related complications.

Survey of newborn direct antiglobulin testing practice in United States and Canadian transfusion services.

BACKGROUND: We hypothesized that variability in practice exists for newborn immunohematology testing due to lack of consensus guidelines. We report the results of a survey assessing that variability at hospitals in the United States and Canada. STUDY DESIGN AND METHODS: An AABB Pediatric Subsection working party developed and validated a survey of newborn immunohematology testing practice. The survey was sent electronically to transfusion service leadership at teaching institutions. RESULTS: The response rate was 67% (61/91); 56 surveys meeting inclusion criteria were analyzed. Approximately 90% (50/56) were from birth hospitals and 16.1% (9/56) were from pediatric hospitals. Newborn immunohematology testing is ordered as a panel by 66.0% (33/50) of birth hospitals. ABO group and DAT is mandated before discharge in 14/56 (25.0%) and 13/56 (23.2%), respectively. About 76.8% (43/56) selectively perform a DAT according to blood blank or clinical parameters. The most common DAT practices include anti-IgG only testing by 73.2% (41/56) and use of umbilical cord specimen type by 67.9% (38/56). A positive DAT is a critical value for 26.8% (15/56) and followed with eluate testing when a maternal antibody screen is positive for 48.2% (27/56). In the setting of a non-ABO maternal red cell antibody, 55.4% (31/56), phenotype neonatal red cells when the DAT is positive. Group O RBC are transfused irrespective of the DAT result for 82.1%, (46/56). CONCLUSION: There is variability in newborn immunohematology testing and transfusion practice and potential overutilization of the DAT. Evidence-based consensus guidelines should be developed to standardize practice and to improve safety.

Distribution of maternal red cell antibodies and the risk of severe alloimmune haemolytic disease of the foetus in a Chinese population: a cohort study on prenatal management.

BACKGROUND: Haemolytic disease of the foetus and newborn (HDFN) is the most common aetiology of haemolytic anaemia and hyperbilirubinaemia in foetuses and neonates. Studies on the distribution of antibodies that cause haemolytic disease of the foetus (HDF) in China are limited, and the effects of multiple antibodies on the severity of HDF need further evaluation. METHODS: An observational cohort study from January 2005 to December 2019 was conducted in two hospitals affiliated with Sun Yat-sen University. Maternal red cell alloimmunization was identified by the Guangzhou Blood Centre. In total, 268 pregnant woman-foetus pairs were divided into four groups according to the type of maternal alloantibodies: anti-D, anti-D combined with other antibodies, other single-antibody and other multiple antibodies. The obstetric history, antibody characteristics, incidence of severe HDF and foetal outcomes were collected and compared. Logistic regression analysis of the risk factors for HDF and survival analysis of the severe HDF-free interval were conducted. RESULTS: Anti-D was the most common cause of HDF, followed by anti-M. No anti-K- or isolated anti-c-associated HDF was found. The incidence of severe HDF was higher in the group with anti-D combined with other antibodies than in the group with anti-D alone (P = 0.025), but no significant difference was found in haemoglobin level and reticulocyte count in the anaemic foetuses between these two groups. Foetuses in the other single-antibody group had a lower reticulocyte count (P = 0.007), more IUTs (P = 0.007) and an earlier onset of severe HDF (P = 0.012). The maximum antibody titre was significantly lower in the other single-antibody group than in the anti-D group (P < 0.001). A high maternal antibody titre (P < 0.001), multiple affected pregnancies (P < 0.001) and other single-antibody (P = 0.042) were independent risk factors for HDF. A higher reticulocyte count (P = 0.041) was an independent risk factor for severe HDF in anaemia foetuses affected by Rh(D) alloimmunization. CONCLUSIONS: The distribution of HDF-associated antibodies in China is different from that in Western countries. Other single non-Rh(D) antibodies could increase the risk of HDF, and anti-D combined with other antibodies would not influence the severity of foetal anaemia compared with anti-D alone.

Red blood cell alloimmunization prevalence and hemolytic disease of the fetus and newborn in Israel: A retrospective study.

Hemolytic disease of the fetus and newborn (HDFN) is a severe form of anemia caused by maternal antibodies against fetal red blood cells (RBC) that can cause intrauterine and perinatal morbidity and mortality. The prevalence and specificities of alloantibodies among Israeli pregnant women and clinical outcomes for their fetuses and newborns are unknown. STUDY DESIGN AND METHODS: A retrospective study of women who gave birth between January 1, 2011, and December 31, 2011, was performed. Data were obtained for obstetric admissions from 16 of 27 hospitals, which included results of maternal ABO, D, antibody screens, antibody identification, and requirements for intrauterine or newborn exchange transfusions. RESULTS: Data on 90 948 women representing 70% of all births during 2011 were analyzed. Antibody screen was positive in 5245 (5.8%) women. Alloantibodies, excluding anti-D titer (<16) were identified in 900 (1.0%) women. Of 191 D- women, 75 (39.3%) had anti-D titer of 16 or greater. Other common clinically significant antibodies were anti-E (204, 23%), anti-K (145, 16%), and anti-c (97, 10.8%) alone or in antibody combinations. Multiple alloantibodies were observed in 132 of 900 (15%) of women. Severe HDFN developed in 6.8% (9/132) of these pregnancies. Seventeen fetuses and newborns (0.02% of births) including one set of twins required RBC transfusions. Two fetuses whose mothers had multiple alloantibodies received intrauterine transfusions; one of them was hydropic and died. CONCLUSION: The prevalence of RBC alloantibodies was 1.0% among Israeli pregnant women. Transfusion was required in 0.02% of the fetuses and newborns. Severe HDFN developed in 6.8% of pregnancies with multiple maternal alloantibodies.