The Spectrum of Hemolytic Disease of the Newborn: Evaluating the Etiology of Unconjugated Hyperbilirubinemia Among Neonates Pertinent to Immunohematological Workup

Abstract

Background and objectiveThe exact burden of hemolytic disease of the newborn (HDN) attributed to neonatal unconjugated hyperbilirubinemia (NUH) in developing nations is still unclear. Still, anti-D is reported to be the most common cause of HDN in India. ABO incompatibility has emerged as a leading cause of exchange transfusion (ET) in many countries. But many centers in our country rely on direct antiglobulin test (DAT) as a screening tool to evaluate immunological causes, whereas advanced immunohematological workup like antibody screening, identification, and elution tests are also required. Early identification of implicated antibodies resulting in HDN can aid in the proper selection of blood units when ET is indicated, and hence also in managing the subsequent pregnancy. This study focused on determining the causes of neonatal hyperbilirubinemia (NH), especially with respect to immunohematological evaluation. This cross-sectional study was conducted on 240 neonates requiring neonatal intensive care unit (NICU) support for NUH at a tertiary care hospital. Materials and methodsDemographic data, along with detailed history pertaining to the cause of hyperbilirubinemia, was collected. Clinical and laboratory evaluation and complete immunohematological work including DAT, heat elution, antibody screening, antibody identification, and Rh Kell phenotyping were performed from neonate blood samples. Data were analyzed using SPSS Statistics version 19 (IBM Corp., Armonk, NY). ResultsPathological jaundice was more common (62.1%) than physiological jaundice (37.9%). The various pathological causes identified were HDN (42.6%), sepsis (12%), cephalohematoma (5.4%), and idiopathic (1.7%). Among HDN cases, ABO incompatibility (39.2%) was the most prevalent cause, followed by Rh HDN and G6PD deficiency (1.7% each). DAT was positive in only 14 cases out of 94 ABO-incompatible cases. Elution revealed antibodies in four DAT-negative neonates with ABO incompatibility and more specificity to the OA setting. DAT was positive with 100% sensitivity in Rh HDN cases (n=4). Elution demonstrated the presence of anti-D (n=2), anti-D + anti-C (n=1) and anti-E (n=1), confirming Rh HDN. DAT strength was found to be significantly associated with hemoglobin (Hb) level (p=0.048). The majority of cases were treated with phototherapy only (94.1%), and 10 cases received both ET and phototherapy. Four neonates' condition improved without any intervention. ConclusionThis study highlighted the shift in the trend from Rh HDN to ABO incompatibility as the cause of hemolytic jaundice in NICU neonates. Elution tests can aid in the diagnosis of DAT-negative ABO-incompatible hemolytic anemia. Early diagnosis, along with timely intervention and appropriate measures, can prevent neonatal morbidity and mortality. Negative DAT does not rule out HDN. Sensitive techniques like elution must be used in the presence of clinical suspicion.

Prevalence of HDNF due to ABO, Rh (D) and Other Blood Groups among Newborns, Sudan

“…Because of the Rh D antigen, HDFN was still existing, as the study showed. Nevertheless, prophylaxis IgG (D) immunoglobulin was utilized; our results are concordant with several previous studies (Bi et al, 2019;Erickson, 2020;Routray et al, 2021). which may indicate improperly or shortage of immunoglobulin dose.…”

“…A diagnosis of ABO HDFN was made in (16.4%), in the current analysis; Bhat YR and Kumar CG, in 2012 (17.3%), agreed with this frequency to the Indian study (Routray et al, 2021) but when Feng CS, Wan CP, et al, who was from Hong Kong, found the incidence of ABO HDFN was 20% among infants with a serum bilirubin level of 300 mmols/L or more, it slightly reduced than frequency (Bi et al, 2019), and our results were slightly lower than this. It may be because their serum bilirubin concentration criteria was short.…”

“…O-A HDFN was less severe than O-B HDFN based on this study, and Kaplan M and Na'amad M agreed with these findings in their study, which supposed that: exchange blood transfusion could be the result of severe hemolysis and severe hemolysis could be caused by anti-B IgG (Ullah et al, 2016). Additionally, YR and Kumar CG's study was contradictory with it, which resulted to an equal incidence in severity being found between them (Routray et al, 2021).…”

Hemolytic Disease of Newborn due to ABO Incompatibility between B Blood Group Mother and A Blood Group Neonate

“…More sensitive tests like heat elution or the Lui's freeze technique can help in negative DAT for better diagnosis of ABO HDN. 9…”

Application of IgG antibody titer and subtype in diagnosis and severity assessment of hemolytic disease of the newborn

“…Among Asian populations, in India there is a high correlation between the rates of prenatal ABO incompatibility and postnatal ABO-HDN incidence. In Singapore, the correlation between prenatal ABO incompatibility rates and postnatal ABO-HDN occurrence is low, and in China ABO incompatibility accounts for 20-25% of mothers and infants (4). Data on the incidence Original Article Application of IgG antibody titer and subtype in diagnosis and severity assessment of hemolytic disease of the newborn of postnatal ABO-HDN also vary, which is believed to account for the 10-20% of ABO incompatibility between mothers and infants, while the incidence of ABO-HDN is reported to be between 2% and 5% (5)(6)(7).…”