Why there is no need to provide RhD immune globulin after spontaneous or induced abortion less than 12 weeks of gestation

When the pregnant women is Rhesus negative and the fetus is Rhesus positive, antibodies might be produced during exchange of blood cells from the fetus to the pregnant women. In a subsequent pregnancy, Rhesus alloimmunization, also known as hemolytic disease of the fetus and newborn (HDFN), can occur due to the presence of these antibodies. Possible effects that might arise are that the child needs to be born prematurely, and severe anemia can be developed and even lead to death of the child.[1] The use of Rh immunoglobulin late in pregnancy and after giving birth has significantly reduced the incidence of haemolytic disease of the foetus and newborn (HDFN) previously responsible for one death in every 2200 births.[2]

In the USA, 15% Caucasians,7% Africans and fewer than 1% Asians are Rh-.[3] Although Rh immunoglobulin  is very safe, hyper sensitivity and anafylactic shock can occur in between  1/10,000 to  1/1000 cases.[4]

While the benefit of using Rh immunoglobulin late in pregnancy and birth is undespesputed, its use for first trimester bleeding is not evidence-based.[5]

Medical abortion makes use of medication to induce the termination of pregnancy. The process of a medical abortion is very similar to a spontaneous abortion.  The home use of abortion pills till 13 weeks is supported by international organisations like the WHO.[6]

Historical evidence that fetal red blood cell (RBC) exposure during early spontaneous or induced abortion can cause maternal Rh sensitization is limited. Two studies that were conducted in 1972, served as the basis for the conservative approach to Rh immunoglobulin administration. These studies  are no longer considered relevant because of the risk of bias but also the surgical techniques used at the time, sharp curettag,  potentially increased the risk of fetal blood exposure and sensitization, which is not the case with the current methods, medical abortion or vaccuum aspirations .

More recent studies indicate that forgoing Rh immunoglobulin administration before 12 weeks gestation is highly unlikely to increase risk of Rh (D) antibody development, and recent studies indicate that fetal RBC exposure during aspiration abortion <12 weeks gestation is below the calculated threshold to cause maternal Rh sensitization.[7]

This is especially important for telemedical abortions services. When using telemedicine, there is no standard determination of bloodtype. The telemedical abortion service Aid Access, only advices people more than 12 weeks pergnant to  determine their blood type and get RhD immune globulin within 72h after the start of bleeding, in line with the recommendations of the Society of fammily planning.

So lets take a closer look at the evidence:

One  study which compared Rh alloimmunization rates between Canada and the Netherlands, offered valuable insights into the real-world impact of Rhogam administration practices. [8]   The populations between Canada and the Netherlands were found to be similar, however there is a difference in practice: Canada recommending Rh immunoglobulin administration and the Netherlands, at the time of this study, offering Rh immunoglobulin to RhD-negative women having spontaneous abortions over 10 weeks’ gestation and induced abortions over 7 weeks. Furthermore, in the Netherlands, where no anti-D immunoglobin is provided routinely in early abortion, showed lower sensitisation rates than Canada. In nearly 2 million blood samples from pregnant women in both Canada and the Netherlands, the prevalence of clinically significant antibodies was statistically lower in the Netherlands: 4.21 (95% CI: 4.12 to 4.30) and 4.03 (95% CI: 3.93 to 4.12) per 1000, respectively. These findings suggested that the differences in Rh testing and immunization protocols between the two countries did not result in significant variations in Rh alloimmunization rates.

A recent prospective study examined 42 pregnant people at 5–12 weeks’ gestational age for the minimum fetal red blood cell concentration required to cause maternal Rh sensitisation.  The study found fetal blood cell exposure in the first trimester to be well below a calculated threshold for Rh sensitisation. [9]

Another recent systematic reviews of Rh immunoprophylaxis found that there is no information at all that would provide evidence for a preventative effect for spontaneous or induced abortion after 8 weeks as these groups  are not represented in the studies [10]

Another systematic review specifically looking into all of published and ongoing studies, concerning RhD-negative individuals seeking abortion at less than 12 weeks’ gestation reveals a paucity of robust evidence supporting routine Rhogam administration in this context.  Despite the theoretical risk of Rh alloimmunization, particularly in subsequent pregnancies, the actual incidence of sensitization following early medical abortions is remarkably low. [11]

Regarding the recent recommendation by the Society for Maternal-Fetal Medicine to provide RhD immune globulin after abortion before 12 weeks' gestation, [12] this goes against recommendations from the Society of Family Planning and the WHO against Rh testing in early pregnancy. [13] 

To illustrate, let's assume a risk of Rh alloimmunization after 7 or 8 weeks of pregnancy.

At this moment approximately 14.000 telemedical services. are  provided every months [14]

Data from Aid Access, a telemedical abortion service, shows that 95% of women seeking their services are under 7 weeks pregnant. Approximately 15% of the US population is Rh-negative. Thus, a small proportion of women seeking telemedical abortion care may be Rh-negative with a Rh-positive fetus. Based on these and other available data, the  calculated risk of Rh sensitization in early abortion is very low, potentially affecting only 0 to 2 out of 14,000 women per month using telemedicine services. [15] [16] [17] This risk is further mitigated by the fact that HDFN is not inherently fatal, with a mortality rate of 1 in every 2200 births.

In  contrast the USA the normal infant mortality rate  beacuse of maternal complications and infections for 2022 is very high : 1 infant deaths per 178 live births .[18]  In contrast, there's a real but low risk of allergic reactions to Rh immunoglobulin, with potentially fatal outcomes. [19]

In conclusion, the debate over Rh immunoglobulin administration in early abortion must consider the evidence and weigh the risks against the benefits. The focus should be on ensuring safe and equitable access to reproductive healthcare, guided by rigorous scientific inquiry.

References:

[1] Rodek C, Deans A. Red cell alloimmunization. In: Rodek CH and Martin JW, editors. Fetal medicine basic sciences and clinical practice, second edition. London: Churchill Livingstone Elsevier; 2009:559-77.

[2] UK National Institute for Health andCare Excellence. Routine antenatalanti-D prophylaxis for women who arerhesus D negative. Technology Appraisal158. 2008

[3] Martin JA, Hamilton BE, Sutton PD,Ventura SJ, Menacker F, Munson ML.Births: final data for 2003.Natl Vital StatRep2005;54:1–116.

[4] https://www.medicines.org.uk/emc/product/6791/smpc#about-medicine

[5] Hannafin B, Lovecchio F, Blackburn P. Do Rh-negative women with first trimester spontaneous abortions need Rh immune globulin? Am J Emerg Med. 2006 Jul;24(4):487-9. doi: 10.1016/j.ajem.2006.01.020. PMID: 16787810.

[6] https://iris.who.int/bitstream/handle/10665/349316/9789240039483-eng.pdf?sequence=1

[7] Horvath S, Goyal V, Traxler S, et al. Society of Family Planning committee consensus on Rh testing in early pregnancy. Contraception. Published online July 21, 2022. doi:org/10.1016/j.contraception.2022.07.002

[8] Wiebe ER, Campbell M, Aiken ARA, 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. 2018 Dec 10;1:100001. doi: 10.1016/j.conx.2018.100001. PMCID: PMC7286179.

[9] Horvath S, Tsao P, Huang Z-Y, 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.

[10] Hamel C, Esmaeilisaraji L, Thuku M, Michaud A, Sikora L, Fung-Kee-Fung K. Antenatal and postpartum prevention of Rh alloimmunization: A systematic review and GRADE analysis. PLoS One. 2020 Sep 10;15(9):e0238844. doi: 10.1371/journal.pone.0238844. PMID: 32913362; PMCID: PMC7482964.

[11] Chan MC, Gill RK, Kim CR. Rhesus isoimmunisation in unsensitised RhD-negative individuals seeking abortion at less than 12 weeks' gestation: a systematic review. BMJ Sex Reprod Health. 2022 Jul;48(3):163-168. doi: 10.1136/bmjsrh-2021-201225. Epub 2021 Nov 24. PMID: 34819315; PMCID: PMC9279745.

[12] Society for Maternal-Fetal Medicine (SMFM), Prabhu M, Louis JM, Kuller JA, SMFM Publications Committee, Society for Maternal-Fetal Medicine Statement: RhD immune globulin after spontaneous or induced abortion less than 12 weeks of gestation, American Journal of Obstetrics and Gynecology (2024), doi: https://doi.org/10.1016/j.ajog.2024.02.288.

[13] https://iris.who.int/bitstream/handle/10665/349316/9789240039483-eng.pdf?sequence=1

[14] https://societyfp.org/wp-content/uploads/2024/02/February-2024-WeCount-Press-Release-1.pdf

[15] Finning KM, Martin PG, Soothill PW, Avent ND. Prediction of fetal D status from maternal plasma: Introduction of a new noninvasive fetal RHD genotyping service. Transfusion. 2002;42(8):1079-1085. doi:10.1046/j.1537-2995.2002.00165.x

[16] Sciellour CR-L, Puillandre P, Gillot R, et al. Large-Scale Pre-Diagnosis Study of Fetal RHD Genotyping by PCR on Plasma DNA from RhD-Negative Pregnant Women. Mol Diagnosis. 2004;8(1):23-31. doi:10.1007/bf03260044

[17] Jabara S, Barnhart KT. Is Rh immune globulin needed in early first-trimester abortion? A review. Am J Obstet Gynecol. 2003;188(3):623-627. doi:10.1067/mob.2003.208

[18] https://www.cdc.gov/nchs/data/vsrr/vsrr033.pdf

[19] https://www.medicines.org.uk/emc/product/6791/smpc#about-medicine