By Katherine Rivlin, MD, MSc
Associate Professor, Department of Obstetrics and Gynecology, University of Chicago
SYNOPSIS: In this multicenter, observational, prospective cohort study, flow cytometry was used to detect circulating fetal red blood cells (fRBCs) in maternal blood among 506 participants before and after induced abortion up to 12 weeks’ gestation. Only three participants had elevated fRBCs at baseline, and only one of these had elevated fRBC counts following the abortion, which indicates that first trimester abortion is not a risk factor for Rh sensitization.
SOURCE: Horvath S, Huang ZY, Koelper NC, et al. Induced abortion and the risk of Rh sensitization. JAMA 2023;330:1167-1174.
The discovery of Rh immunoglobulin to treat Rh-negative patients in term pregnancies dramatically reduced the risk of Rh sensitization. The benefits of this intervention are vast, since alloimmunization from prior pregnancy can lead to devastating outcomes, including hemolytic disease of the newborn. However, population-based studies have never shown that routinely administering Rh immunoglobulin to Rh-negative patients in the first trimester reduces the incidence of Rh sensitization.1 Both Rh testing and Rh immunoglobulin administration are costly, time-intensive, and unnecessary, and potentially painful phlebotomy and injections are not patient-centered. Without clear evidence, guidelines that recommend Rh testing and administration are based on theoretical concerns. Routine testing has only been incorporated into practice in countries with the resources to do so. Given the concern that such guidelines reduce access with no clear benefit, the World Health Organization (WHO) recommended against Rh testing during the first trimester in 2022.2 Since that time, national and international guidelines have conflicted, which confuses providers and patients and makes changes to clinical practice challenging.3,4
Historically, laboratory techniques have had inadequate sensitivity to detect low levels of Rh, which has made detecting the threshold of fRBCs needed to cause sensitization hard to measure. A pilot study indicated that refined flow cytometry can reliably detect fRBCs well below this threshold.5 Horvath et al aimed to determine whether levels of fRBCs in maternal circulation remain below the sensitization threshold among individuals undergoing abortion before 12 weeks. The study team initially recruited all patients undergoing medication abortion up to 12 weeks’ gestation at four clinical sites. They expanded recruitment to include procedural abortion to improve generalizability and to improve recruitment during the COVID-19 pandemic. They excluded patients with sickle cell disease, beta thalassemia, hereditary persistence of fetal hemoglobin or other hemoglobinopathies, and those who opted not to participate in follow-up.
The team obtained blood type and Rh status from the electronic medical record, and patients self-reported their demographics. The primary outcome of interest was the number of participants whose fRBC counts crossed the sensitization threshold of 125 fRBCs/5 million total RBCs. Secondarily, they measured differences in fRBC counts before and after abortion care, differences in fRBCs by weeks’ gestation, and by other maternal characteristics. They aimed to recruit 500 participants to reject the null hypothesis that 1.5% or more of the post-abortion population had fRBC counts exceeding the threshold. This sample size would require fewer than four participants
(< 0.8%) to exceed the threshold to reject the null hypothesis.
Between July 2019 and July 2022, they consented 644 individuals and obtained phlebotomy specimens from 506 participants. Among their participants, the mean age was 27.4 years (standard deviation, 5.5), 61.9% were Black, and 24.3% were white. Most (90%) were Rh positive, some (19%) reported prior bleeding in pregnancy, and most (63%) underwent medication abortion. No participant had a newly elevated fRBC count above the threshold, and only one participant exceeded the threshold of 125 fRBCs after abortion. That individual participant underwent a medication abortion, had an AB+ blood type, and reported having experienced bleeding earlier in the pregnancy. In addition, this individual was among a cohort of 13 participants whose flow cytometry assay had not undergone optimization. No individual exceeded the threshold using the optimized assay. The median fRBC count in the study cohort after abortion was 4.5/5 million cells.
Although the team found a strong association between pre-abortion and post-abortion fRBC counts, they found no other maternal characteristic significantly associated with post-abortion fRBC count. This included having bleeding previously in pregnancy. They also found no significant increase in fRBC count with increasing gestational stage (P = 0.14).
COMMENTARY
This study takes advantage of modern technologies unavailable at the time of Rh immunoglobulin discovery to better quantify maternal exposure to fRBC. The reassuring findings indicate that Rh sensitization in the first trimester of pregnancy is highly unlikely, and that Rh testing and Rh immune globulin administration is not necessary prior to induced abortion up to 12 weeks of pregnancy.
The authors stated that although this study was performed in a patient population undergoing induced abortion, its findings also are generalizable to other bleeding events in early pregnancy, including spontaneous abortion and threatened abortion. Miscarriage is managed similarly to abortion, and the risk of maternal-fetal hemorrhage is lower in miscarriage compared to induced abortion following the loss of fetal circulatory activity. The lack of increased fRBCs counts among participants with prior bleeding in pregnancy provides additional support for foregoing Rh testing and immunoglobulin administration in the context of early pregnancy loss.
The study did not include ectopic pregnancy or molar pregnancy; therefore, its findings cannot be generalized to those clinical scenarios. However, the study had narrow exclusions, allowing for clinical scenarios that reflect the realities of clinical care, such as a range of blood types, gestational stages, abortion methods, and for the presence of prior bleeding in pregnancy in some participants. This ensures that its findings can easily be incorporated into clinical practice. Similarly, national and international guidelines now can align with the WHO recommendations to forego Rh testing before 12 weeks of pregnancy. This shift in guidelines is of particular importance given the loss of access to in-person abortion care in large swaths of the United States following the Supreme Court Dobbs decision. Now more than ever, the need for efficient, evidence-based, and patient-centered abortion care that foregoes unnecessary testing, cost, and intervention is paramount.
REFERENCES
- Wiebe ER, Campbell M, Aiken AR, Albert A. Can we safely stop testing for Rh status and immunizing Rh-negative women having early abortions? A comparison of Rh alloimmunization in Canada and the Netherlands. Contracept X 2019;1:100001.
- World Health Organization. Abortion Care Guideline. World Health Organization; 2022. https://www.who.int/publications/i/item/9789240039483
- [No authors listed]. Practice Bulletin No. 181: Prevention of Rh D alloimmunization. Obstet Gynecol 2017;130:e57-e70.
- Horvath S, Goyal V, Traxler S, Prager S. Society of Family Planning committee consensus on Rh testing in early pregnancy. Contraception 2022;114:1-5.
- Horvath S, Tsao P, Huang ZY, et al. The concentration of fetal red blood cells in first-trimester pregnant women undergoing uterine aspiration is below the calculated threshold for Rh sensitization. Contraception 2020;102:1-6.
