References
American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin No. 181: Prevention of Rh D Alloimmunization. Obstet Gynecol. 2017;130(2):e57–e70. doi:10.1097/AOG.0000000000002232
American College of Obstetricians and Gynecologists (ACOG). Rh D immune globulin administration after abortion or pregnancy loss at less than 12 weeks of gestation. Obstet Gynecol. 2024;144(6):e140–e143. doi:10.1097/AOG.0000000000005733
Fung-Kee-Fung K, Wong K, Walsh J, Hamel C, Clarke G. Guideline No. 448: prevention of Rh D alloimmunisation. J Obstet Gynaecol Can. 2024;46:102449. doi:10.1016/j.jogc.2024.102449
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. doi:10.1016/j.contraception.2022.07.002
Horvath S, Huang ZY, Koelper NC, Martinez C, Tsao PY, Zhao L, Goldberg AB, Hannum C, Putt ME, Luning Prak ET, Schreiber CA. Induced Abortion and the Risk of Rh Sensitization. JAMA. 2023 Sep 26;330(12):1167-1174. doi: 10.1001/jama.2023.16953.
Horvath S, Tsao P, Huang Z, Zhao L, Du Y, Sammel MD, et al. The concentration of fetal red blood cells in first-trimester pregnant women undergoing uterine aspiration is below the calculated threshold for Rh sensitisation. Contraception. 2020;102:1–6. doi:10.1016/j.contraception.2020.02.011
Horvath S, Goyal V, Traxler S, Prager S. Society of Family Planning committee consensus on Rh testing in early pregnancy. Contraception. 2022 Oct;114:1-5. doi: 10.1016/j.contraception.2022.07.002.
International Federation of Gynecology and Obstetrics (FIGO). FIGO consensus statement: uterine evacuation. London (UK): FIGO; 2020 [updated 2020 Feb 10; cited 2025 Jul 24]. Available from: https://www.figo.org/news/figo-consensus-statement-uterine-evacuation
Karanth L, Musini VM, Alfirevic Z. Anti-D administration after spontaneous miscarriage for preventing Rh alloimmunisation. Cochrane Database Syst Rev. 2013;(3):CD002847. doi:10.1002/14651858.CD002847.pub3
Klein HG, Anstee DJ. Mollison’s blood transfusion in clinical medicine. 12th ed. Wiley-Blackwell; 2014.
National Abortion Federation. Clinical policy guidelines for abortion care. 2024 [cited 2025 Jul 24]. Available from: https://prochoice.org/providers/quality-standards/
National Institute for Health and Care Excellence (NICE). Abortion care. NICE guideline [NG140]. 2019. Available from: https://www.nice.org.uk/guidance/ng140
National Institute for Health and Care Excellence (NICE). Ectopic pregnancy and miscarriage. NICE guideline [NG126]. 2021. Available from: https://www.nice.org.uk/guidance/ng126
Prabhu M, Louis JM, Kuller JA. Society for Maternal-Fetal Medicine statement (SMFM): RhD immune globulin after spontaneous or induced abortion at less than 12 weeks of gestation. Am J Obstet Gynecol. 2024;230:B2–5. doi:10.1016/j.ajog.2024.02.288
Queenan JT, Gadow EC, Lopes AC. Role of spontaneous abortion in Rh immunization. Am J Obstet Gynecol. 1971;110(1):128–130.
Royal College of Obstetricians and Gynaecologists (RCOG). Best practice in abortion care. London: RCOG; 2022 [cited 2025 Jul 24]. Available from: https://www.rcog.org.uk/media/geify5bx/abortion-care-best-practice-paper-april-2022.pdf
Schmidt-Hansen M, Lord J, Hawkins J, Cameron S, Pandey A, Hasler E, Regan F. Anti-D prophylaxis for rhesus D (RhD)-negative women having an abortion of a pregnancy up to 13+6 weeks’ gestation: a systematic review and new NICE consensus guidelines. BMJ Sex Reprod Health. 2020 Jan 20:bmjsrh-2019-200536. doi: 10.1136/bmjsrh-2019-200536.
Urbaniak SJ. Rh prophylaxis: Where are we now? Semin Hematol. 1998;35(3):230–43..
Visscher RD, Visscher HC. Do Rh-negative women with an early spontaneous abortion need Rh immune prophylaxis? Am J Obstet Gynecol. 1972;113(2):230–233.
Visser GHA, Thommesen T, Di Renzo GC, Nassar AH, Spitalnik SL; FIGO Committee for Safe Motherhood, Newborn Health. FIGO/ICM guidelines for preventing Rhesus disease: A call to action. Int J Gynaecol Obstet. 2021 Feb;152(2):144-147. doi: 10.1002/ijgo.13459.
Wiebe ER, Campbell M, Aiken AR, Albert A. Can we safely stop testing for Rh status and immunising RhD-negative women having early abortions? A comparison of Rh alloimmunisation in Canada and the Netherlands. Contracept X. 2018;1:100001. doi:10.1016/j.conx.2018.100001
World Health Organization (WHO). Abortion care guideline. Geneva: WHO; 2022 [cited 2025 Jul 24]. Available from: https://iris.who.int/bitstream/handle/10665/349316/9789240039483-eng.pdf
Molar Pregnancies
Guidelines are consistent in recommending RhIg in cases of a confirmed diagnosis of complete molar pregnancy, where its use is not recommended. This is because organogenesis does not occur in such cases, meaning that Rh sensitisation cannot occur.
The situation is more complex in the case of partial molar pregnancies, as organogenesis occurs at least partially, and the theoretical risk of sensitisation cannot be excluded. Furthermore, distinguishing between the two types can be challenging, and in cases of uncertain diagnosis, a mole is treated as partial for the purpose of evaluating potential RhIg administration.
The FIGO guidelines (2021) merely state that RhIg is generally administered in such cases, referencing ACOG Practice Bulletin No. 181 (2017), but do not provide an explicit formal recommendation on its use in this context. The SOGC (2024) advises against RhIg administration in molar pregnancies before 8 weeks of gestation and suggests that its use between 8 and 12 weeks may be considered only in women at increased risk. RhIg is recommended after 12 weeks at a dose of 300 μg. The SOGC 2024 recommends not administering RhIg in molar pregnancy before 8 weeks and suggests not administering it between 8 and 12 weeks, unless the patient is considered at higher risk. After 12 weeks, administration of 300 μg of RhIg is suggested (SOGC, 2024).
References
American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin No. 181: Prevention of Rh D Alloimmunization. Obstet Gynecol. 2017;130(2):e57–e70. doi:10.1097/AOG.0000000000002232
American College of Obstetricians and Gynecologists (ACOG). Rh D immune globulin administration after abortion or pregnancy loss at less than 12 weeks of gestation. Obstet Gynecol. 2024;144(6):e140–e143. doi:10.1097/AOG.0000000000005733
Fung-Kee-Fung K, Wong K, Walsh J, Hamel C, Clarke G. Guideline No. 448: prevention of Rh D alloimmunisation. J Obstet Gynaecol Can. 2024;46:102449. doi:10.1016/j.jogc.2024.102449
Visser GHA, Thommesen T, Di Renzo GC, Nassar AH, Spitalnik SL; FIGO Committee for Safe Motherhood, Newborn Health. FIGO/ICM guidelines for preventing Rhesus disease: A call to action. Int J Gynaecol Obstet. 2021 Feb;152(2):144-147. doi: 10.1002/ijgo.13459.
Amniocentesis, Cordocentesi e Chorionic villous sampling
The SOGC (2024) guidelines recommend administration of RhIg at a minimum dose of 120 μg following chorionic villous sampling during the first 12 weeks of gestation in non-sensitized RhD-negative women. For invasive procedures such as amniocentesis, chorionic villus sampling, and cordocentesis performed during the second or third trimester, a dose of 300 μg is recommended.
FIGO (2021) recommends RhIg following amniocentesis and chorionic villus sampling, at a dose of 500 IU (100 μg).
Similarly, ACOG (2016) recommends RhIg administration for all RhD-negative women undergoing invasive diagnostic procedures such as chorionic villus sampling or amniocentesis when the fetus is, or may be, RhD-positive. ACOG does not specify a preferred dose but refers to other clinical guidelines that suggest administering either 125 μg or 300 μg depending on gestational age.
Since cordocentesis, among the procedures discussed, poses the highest risk of FMH exceeding 30 mL due to the potential for significant placental trauma and disruption, the SOGC explicitly recommends FMH testing in this context, specifying that if the FMH volume exceeds that covered by the standard RhIg dose, an additional 10 μg of RhIg should be administered for every 0.5 mL of fRBCs.
References
American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin No. 181: Prevention of Rh D Alloimmunization. Obstet Gynecol. 2017;130(2):e57–e70. doi:10.1097/AOG.0000000000002232
Fung-Kee-Fung K, Wong K, Walsh J, Hamel C, Clarke G. Guideline No. 448: prevention of Rh D alloimmunisation. J Obstet Gynaecol Can. 2024;46:102449. doi:10.1016/j.jogc.2024.102449
Visser GHA, Thommesen T, Di Renzo GC, Nassar AH, Spitalnik SL; FIGO Committee for Safe Motherhood, Newborn Health. FIGO/ICM guidelines for preventing Rhesus disease: A call to action. Int J Gynaecol Obstet. 2021 Feb;152(2):144-147. doi: 10.1002/ijgo.13459.
Intrauterine foetal death
FIGO (2021) recommends the administration of RhIg (500 or 1500 IU; equivalent to 100 or 300 µg) following intrauterine foetal death in the second or third trimester of pregnancy. Similarly, ACOG (2017) advises that RhD-negative individuals should receive RhIg after foetal death occurring beyond the first trimester.
To guide RhIg dosing, FIGO (2021) supports using the Kleihauer–Betke test to quantify FMH. ACOG (2017) firmly recommends screening for significant FMH at the time of diagnosis to determine whether additional RhIg is needed.
References
American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin No. 181: Prevention of Rh D Alloimmunization. Obstet Gynecol. 2017;130(2):e57–e70. doi:10.1097/AOG.0000000000002232
Fung-Kee-Fung K, Wong K, Walsh J, Hamel C, Clarke G. Guideline No. 448: prevention of Rh D alloimmunisation. J Obstet Gynaecol Can. 2024;46:102449. doi:10.1016/j.jogc.2024.102449
Visser GHA, Thommesen T, Di Renzo GC, Nassar AH, Spitalnik SL; FIGO Committee for Safe Motherhood, Newborn Health. FIGO/ICM guidelines for preventing Rhesus disease: A call to action. Int J Gynaecol Obstet. 2021 Feb;152(2):144-147. doi: 10.1002/ijgo.13459.
Abdominal trauma
FIGO (2021) recommends the administration of RhIg following abdominal trauma occurring during the second or third trimester of pregnancy. Although the precise risk of alloimmunisation and the optimal dose remain uncertain, FIGO advises the use of RhIg in such cases, noting that 1500 IU (300 µg) is the dose most frequently used, although 500 IU (100 µg) is also acceptable.
ACOG (2017) also recommends administering anti-D immune globulin to RhD-negative women who have experienced abdominal trauma.
Regarding FMH testing, FIGO highlights that while no specific dose of RhIg has been definitively established for use after abdominal trauma, the Kleihauer–Betke test is considered highly useful in such circumstances and can be employed to guide appropriate dosing based on the estimated volume of fetomaternal haemorrhage. Correspondingly, ACOG advises quantifying FMH to determine whether additional doses of RhIg are necessary.
References
American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin No. 181: Prevention of Rh D Alloimmunization. Obstet Gynecol. 2017;130(2):e57–e70. doi:10.1097/AOG.0000000000002232
Fung-Kee-Fung K, Wong K, Walsh J, Hamel C, Clarke G. Guideline No. 448: prevention of Rh D alloimmunisation. J Obstet Gynaecol Can. 2024;46:102449. doi:10.1016/j.jogc.2024.102449
Visser GHA, Thommesen T, Di Renzo GC, Nassar AH, Spitalnik SL; FIGO Committee for Safe Motherhood, Newborn Health. FIGO/ICM guidelines for preventing Rhesus disease: A call to action. Int J Gynaecol Obstet. 2021 Feb;152(2):144-147. doi: 10.1002/ijgo.13459.
External Cephalic Version in Breech Presentation
The volume of fetomaternal haemorrhage (FMH) occurring during external cephalic version (ECV) is generally regarded as minimal. This assertion is substantiated by a large-scale Canadian study which determined that the routine administration of RhIg at approximately 32 weeks’ gestation is adequate to prevent alloimmunisation following ECV (Boucher, Marquette, Varin, Champagne, & Bujold, 2008).
However, considering that the estimated incidence of FMH during ECV ranges from 1.8% to 6% (Boucher et al., 2008; Marcus, Crewe-Brown, Krawitz, & Katz, 1975; Lau, Stock, & Rogers, 1995), current guidelines vary with respect to anti-D prophylaxis. The Society of Obstetricians and Gynaecologists of Canada (SOGC, 2024) recommends the administration of RhIg at a dose of 300 µg following ECV. Conversely, the International Federation of Gynecology and Obstetrics (FIGO, 2021) advises a lower dose of 500 IU (equivalent to 100 µg), while the American College of Obstetricians and Gynecologists (ACOG) endorses RhIg administration post-ECV without specifying an exact dosage.
References
American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin No. 181: Prevention of Rh D Alloimmunization. Obstet Gynecol. 2017;130(2):e57–e70. doi:10.1097/AOG.0000000000002232
Boucher M, Marquette GP, Varin J, Champagne J, Bujold E. Fetomaternal hemorrhage during external cephalic version. Obstet Gynecol. 2008 Jul;112(1):79-84. doi: 10.1097/AOG.0b013e318179978c.
Fung-Kee-Fung K, Wong K, Walsh J, Hamel C, Clarke G. Guideline No. 448: prevention of Rh D alloimmunisation. J Obstet Gynaecol Can. 2024;46:102449. doi:10.1016/j.jogc.2024.102449
Marcus RG, Crewe-Brown H, Krawitz S, Katz J. Feto-maternal haemorrhage following successful and unsuccessful attempts at external cephalic version. Br J Obstet Gynaecol. 1975 Jul;82(7):578-80. doi: 10.1111/j.1471-0528.1975.tb00690.x.
Lau TK, Stock A, Rogers M. Fetomaternal haemorrhage after external cephalic version at term. Aust N Z J Obstet Gynaecol. 1995 May;35(2):173-4. doi: 10.1111/j.1479-828x.1995.tb01862.x.
Visser GHA, Thommesen T, Di Renzo GC, Nassar AH, Spitalnik SL; FIGO Committee for Safe Motherhood, Newborn Health. FIGO/ICM guidelines for preventing Rhesus disease: A call to action. Int J Gynaecol Obstet. 2021 Feb;152(2):144-147. doi: 10.1002/ijgo.13459.
Delivery and postpartum
The baseline risk of detecting postpartum alloimmunisation in Rh-negative women who have delivered RhD-positive infants has been calculated to be 7% at 6 months postpartum (Pollack et al., 1968) and up to 17% in subsequent pregnancies (Ascari et al., 1969). Administration of RhIg in these women significantly reduces the risk of maternal sensitisation and subsequent haemolytic disease of the foetus and newborn (HDFN) in future pregnancies. Evidence from various study types consistently demonstrates that postpartum RhIg reduces the rate of alloimmunisation from approximately 13–16% to 0.5–1.8% (de Haas et al., 2014; Bowman, 2003). A systematic review has shown that RhIg administration within 24–72 hours of delivery significantly reduces sensitisation both at 6 months postpartum (absolute risk reduction [ARR]: 70 per 1000; 95% confidence interval [CI]: 67–71) and in subsequent pregnancies (ARR: 130 per 1000; 95% CI: 117–139) (Hamel et al., 2020).
All guidelines are consistent in strongly recommending routine administration of RhIg for all unsensitised Rh-negative women who have delivered a RhD-positive infant. Some variation exists regarding the optimal dosing, although all guidelines advise against very low doses (e.g., 50 µg), as the prophylactic efficacy of RhIg is dose-dependent and under-dosing may increase the risk of alloimmunisation (Crowther & Middleton, 2000).
The median volume of FMH at delivery is approximately 0.7 mL (Lubusky et al., 2012). It has been calculated that each 10 µg (50 IU) of RhIg provides protection against approximately 0.5 mL of RhD-positive FRBCs in the maternal circulation, equivalent to 1 mL of whole foetal blood (Lubusky et al., 2012; Bowman, 1985). Therefore, according to the doses most frequently recommended in clinical guidelines: 500 IU of RhIg protects against up to 10 mL of FMH, 120 µg (approximately 600 IU) up to 12 mL, and 300 µg (approximately 1500 IU) up to 30 mL. While a dose of 500 IU has been considered adequate, a recent meta-analysis suggests that the 1500 IU regimen may offer slightly higher efficacy (Xie et al., 2020). As current evidence does not definitively establish the optimal standard dose of RhIg, guidelines vary in their dosing recommendations. For example, the SOGC recommends administering either 120 μg or 300 μg of RhIg.
Moreover, since the volume of FMH sufficient to trigger RhD alloimmunisation can range from as little as 0.1 mL to as much as 30 mL (Bowman, 1988; Von Stein et al., 1992), routine quantification is particularly valuable when high-volume FMH is suspected (Giouleka et al., 2024; Lubusky et al., 2012) but may also offer benefit for all Rh-negative women. Indeed, limiting FMH testing to women with overt clinical risk factors, such as abruptio placentae, placenta praevia, intrauterine manipulation, or intrauterine foetal death, fails to identify a substantial proportion of women requiring more than the standard RhIg dose (Welsh & Bai, 2016), with up to 50% of such cases potentially remaining unrecognised (Ness et al., 1987). For these reasons, FMH testing, typically performed using the Kleihauer–Betke test or flow cytometry, is recommended, or at least suggested, in most international guidelines, including those issued by the British Committee for Standards in Haematology (BCSH), the Royal College of Obstetricians and Gynaecologists (RCOG), and the Society of Obstetricians and Gynaecologists of Canada (SOGC). Notably, ACOG has recommended since 2017 that all RhD-negative women giving birth to RhD-positive infants undergo FMH testing, starting with a qualitative screening method such as the rosette test and, if indicated, proceeding to quantitative testing such as the Kleihauer–Betke test to determine the number of additional RhIg doses required.
Moreover, as FMH testing is increasingly recommended for all RhD-negative women who give birth to RhD-positive infants, and as evidence suggests that caesarean section does not increase the risk of high-volume FMH (Lubusky et al., 2012), the previous practice of routinely administering additional RhIg following caesarean delivery has been withdrawn. The current approach bases the need for any supplemental RhIg solely on the outcome of FMH testing.
Whenever FMH testing reveals a volume exceeding that covered by the standard postpartum dose of RhIg, additional doses are recommended. For example, the SOGC recommends administering 120 μg of RhIg for FMH volumes less than 12 mL, 300 μg for volumes between 12 and 30 mL, and 10 μg more for each milliliter above 30 mL of FMH.
All clinical guidelines advise administering RhIg as soon as possible following a potentially sensitising event, such as delivery, and concur that the optimal timing for anti-D immune globulin administration is within the standard 72-hour window. However, both the SOGC and ACOG acknowledge evidence supporting the effectiveness of RhIg administration up to 13 days post-exposure (Samson et al., 1975), and other sources suggest potential benefit when administered as late as 28 days postpartum (Bowman, 1985; Fung Kee Fung et al., 2003). Based on this evidence, the SOGC strongly recommends administering a 300 μg dose of RhIg as soon as the need is identified, for up to 28 days after delivery, if the standard 72-hour window has been missed.
References
Ascari WQ, Levine P, Pollack W. Incidence of maternal Rh immunization by ABO compatible and incompatible pregnancies. Br Med J. 1969 Feb 15;1(5641):399-401. Doi: 10.1136/bmj.1.5641.399.
Bowman JM. Controversies in Rh prophylaxis. Who needs Rh immune globulin and when should it be given? Am J Obstet Gynecol. 1985 Feb 1;151(3):289-94. Doi: 10.1016/0002-9378(85)90288-1.
Bowman JM. The prevention of Rh immunization. Transfus Med Rev. 1988 Sep;2(3):129-50. Doi: 10.1016/s0887-7963(88)70039-5. PMID: 2856526.
Bowman J. Thirty-five years of Rh prophylaxis. Transfusion. 2003 Dec;43(12):1661-6. Doi: 10.1111/j.0041-1132.2003.00632.x.
Crowther C, Middleton P. Anti-D administration after childbirth for preventing Rhesus ensitizationon. Cochrane Database Syst Rev. 2000;1997(2):CD000021. Doi: 10.1002/14651858.CD000021.
de Haas M, Finning K, Massey E, Roberts DJ. Anti-D prophylaxis: past, present and future. Transfus Med. 2014 Feb;24(1):1-7. Doi: 10.1111/tme.12099.
Fung Kee Fung K, Eason E, Crane J, Armson A, De La Ronde S, Farine D, Keenan-Lindsay L, Leduc L, Reid GJ, Aerde JV, Wilson RD, Davies G, Désilets VA, Summers A, Wyatt P, Young DC; Maternal-Fetal Medicine Committee, Genetics Committee. Prevention of Rh alloimmunization. J Obstet Gynaecol Can. 2003 Sep;25(9):765-73. Doi: 10.1016/s1701-2163(16)31006-4.
Giouleka S, Tsakiridis I, Kostakis N, Boureka E, Mamopoulos A, Kalogiannidis I, Athanasiadis A, Dagklis T. Postnatal Care: A Comparative Review of Guidelines. Obstet Gynecol Surv. 2024 Feb;79(2):105-121. Doi: 10.1097/OGX.0000000000001224.
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.
Lubusky M, Simetka O, Studnickova M, Prochazka M, Ordeltova M, Vomackova K. Fetomaternal hemorrhage in normal vaginal delivery and in delivery by cesarean section. Transfusion. 2012 Sep;52(9):1977-82. Doi: 10.1111/j.1537-2995.2011.03536.x.
Ness PM, Baldwin ML, Niebyl JR. Clinical high-risk designation does not predict excess fetal-maternal hemorrhage. Am J Obstet Gynecol. 1987 Jan;156(1):154-8. doi: 10.1016/0002-9378(87)90228-6.
Pollack W, Gorman JG, Freda VJ, Ascari WQ, Allen AE, Baker WJ. Results of clinical trials of RhoGAM in women. Transfusion. 1968 May-Jun;8(3):151-3. Doi: 10.1111/j.1537-2995.1968.tb04895.x. PMID: 4173363.
Samson D, Mollison PL. Effect on primary Rh immunization of delayed administration of anti-Rh. Immunology. 1975 Feb;28(2):349-57.
Sebring ES, Polesky HF. Fetomaternal hemorrhage: incidence, risk factors, time of occurrence, and clinical effects. Transfusion. 1990 May;30(4):344-57. Doi: 10.1046/j.1537-2995.1990.30490273444.x.
Von Stein GA, Munsick RA, Stiver K, Ryder K. Fetomaternal hemorrhage in threatened abortion. Obstet Gynecol. 1992 Mar;79(3):383-6. Doi: 10.1097/00006250-199203000-00011.
Welsh KJ, Bai Y; Education Committee of the Academy of Clinical Laboratory Physicians and Scientists. Pathology Consultation on Patients With a Large Rh Immune Globulin Dose Requirement. Am J Clin Pathol. 2016 Jun;145(6):744-51. Doi: 10.1093/ajcp/aqw051.