title: Intravenous drug use is associated with alloimmunization in pregnancy.
abstract: Anecdotal evidence has suggested an association of intravenous drug abuse with alloimmunization; however, published data are limited to case reports.
  
  
  
  The purpose of this study was to determine whether women with a history of intravenous drug abuse have an increased risk of alloimmunization.
  
  
  
  A retrospective cohort study was performed with the use of data from a single-center blood bank and perinatal database from 2008-2014. Blood bank data were used to identify women with alloimmunization, which was defined as a positive antibody screen in pregnancy not due to naturally occurring antibodies, agglutinins, autoantibodies, or Rh immunoglobulin administration. Intravenous drug abuse was ascertained from a comprehensive database that has captured all drug abuse in pregnancy since 2008. For women who contributed >1 pregnancy to the database, only the most recent pregnancy was included. The rates of alloimmunization among women with a history of intravenous drug abuse and general obstetric populations were calculated and compared. The distribution of alloantibody types, proportion of Rh-group alloantibodies, and patient Rh status were assessed for intravenous and non-intravenous drug abuse-associated alloimmunization. Characteristics and outcomes between intravenous and non-intravenous drug abuse-associated alloimmunization were assessed for women with clinically significant alloantibodies.
  
  
  
  Alloimmunization was more common in women with a history of intravenous drug abuse (11/305 women; 3.6%) compared to women without a history of intravenous drug abuse (288/16,022 women; 1.8%; relative risk, 2.00; 95% confidence interval, 1.11-3.62). Needle-sharing was present in 7 and suspected in 4 women with an intravenous drug abuse history. Among women with a history of intravenous drug abuse, none had a history of transfusion or traditional risk factor for alloimmunization. The distribution of alloantibodies was different between intravenous drug abuse- and non-intravenous drug abuse-associated alloimmunization. Rh group alloantibodies and Rh-negative status were more common in women with a history of intravenous drug abuse. Among Rh-negative women with a history of intravenous drug abuse, 50% of RhD alloimmunization cases occurred in nulliparous women. The rate of multiple alloantibodies was not different between intravenous drug abuse- and non-intravenous drug abuse-associated alloimmunization.
  
  
  
  Maternal history of intravenous drug abuse is associated with an increased risk of alloimmunization. Approximately 1 in 30 intravenous drug abuse women may be diagnosed with an alloantibody in pregnancy. Given the current US opioid epidemic, increased vigilance in screening is required. Needle-sharing represents a possible mechanism for intravenous drug abuse-associated alloimmunization; however, limited obstetric care, failure to obtain Rh immunoglobulin, or failure to identify early pregnancy loss cannot be excluded.
authors.affiliation: Division of Maternal Fetal Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH. Electronic address: jlappen@metrohealth.org.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Lappen
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, OH.
authors.forename: Sydney
authors.initials: S
authors.lastname: Stark
authors.affiliation: Division of Maternal Fetal Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH.
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Gibson
authors.affiliation: Ohio State University College of Medicine and Mt. Carmel Medical Center, Columbus, OH.
authors.forename: Mona
authors.initials: M
authors.lastname: Prasad
authors.affiliation: Division of Maternal Fetal Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bailit
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007518:Isoantibodies / Q000032:analysis*; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood*; D012189:Retrospective Studies; D012204:Rh-Hr Blood-Group System / Q000276:immunology*; D015819:Substance Abuse, Intravenous / Q000150:complications*
chemical_list: D007518:Isoantibodies; D012204:Rh-Hr Blood-Group System
keywords: alloantibodies; alloimmunization; hemolytic disease of the fetus and newborn infant; intravenous drug use; pregnancy