IV drug abuse linked to alloimmunization

Women with a history of intravenous (IV) drug abuse appear to be at increased risk of having a pregnancy complicated by red cell alloimmunization, according to results of a recently published retrospective study. Appearing March 17, 2016, online in the American Journal of Obstetrics and Gynecology, the study’s findings are relevant and concerning considering that opioid addiction and heroin abuse are a growing epidemic in the United States, said lead author Justin Lappen, MD.

“An association between intravenous drug abuse and alloimmunization has been previously described in published case reports and small case series. Our study, however, represents the first study to explore this issue in a large obstetric cohort using an appropriate comparison group,” said Dr. Lappen, Maternal Fetal Medicine Fellow and Assistant Professor, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.

“Our research has some limitations relating to its relatively small sample size and retrospective design, and certainly further investigation is warranted to confirm our results. Nevertheless, we believe that our findings support intensified efforts towards establishing prenatal care early for women with a history of intravenous drug abuse and increasing screening for alloantibodies, whose presence has implications for hemolytic disease as well as transfusion medicine, both of which can impact maternal and neonatal outcomes”

For the study information about alloimmunization and IV drug abuse among pregnant women was extracted from MetroHealth Medical Center’s blood bank, perinatal, and Mother and Child Dependency Program databases for the years 2008 to 2014. The analyses included 305 women with a history of IV drug abuse and 16,022 women without such a history. Relative to the control population, the IV drug abuse group had a two-fold higher relative risk of alloimmunization (3.6% vs 1.8%), which was statistically significant. The women who were IV drug abusers were also significantly more likely to be Rh-negative than the control group (45.5% vs 9.4%; P = .003) and to have antibodies against Rh group antigens (72.7% vs 29.2%; P = .004). Other analyses identified trends for the IV drug abusers to more often have multiple alloantibodies (27.2% vs 8.0%; P = .06), a critical titer (50.0% vs 19.2%; P = .06), and a newborn infant with hemolytic disease (25% vs 6.7%; P = .012). Inadequate study power may explain failure to achieve a statistically significant difference between groups in those outcomes, said Dr. Lappen.

Due to limitations in its design and the data sources used, the study could not exclude the contribution of limited obstetric care in a vulnerable population to the higher alloimmunization rate in the IV drug abuse group, such as undocumented early pregnancy loss or failure to obtain Rhogam. However, several findings support the idea that sensitization occurred as a result of exposure to foreign red cell antigens secondary to IV drug injection. First, all 11 women who were IV drug abusers were known or suspected to have shared needles. In addition, none had a history of transfusion or other traditional risk factors for alloimmunization.

While not statistically significant, Dr. Lappen noted that the findings that women who were IV drug abusers more often had multiple alloantibodies and more often had a critical titer than the control group are also concerning and may highlight the impact of repeated antigen exposure through IV drug abuse. These factors may increase the risk of an adverse fetal outcome, or theoretically could result in sensitization and an affected newborn in a first pregnancy. “In our study, half of the intravenous drug users with Rh-alloimmunization were thought to be in their first pregnancy,” said Dr. Lappen.

“Although it was not possible to confirm this history using the available data sources, we hope to better investigate the risk of alloimmunization in nulliparous women in the future in order to determine if intravenous drug injection with shared needles places them at increased risk of reaching a critical antibody titer or having a fetus or baby with hemolytic anemia.”