Do Rh-negative women with first trimester spontaneous abortions need Rh immune globulin?

doi:10.1016/j.ajem.2006.01.020

The American Journal of Emergency Medicine

Volume 24, Issue 4, July 2006, Pages 487-489

https://doi.org/10.1016/j.ajem.2006.01.020 Get rights and content

Abstract

Objective

To examine whether literature supports the use of Rh immune globulin in Rh-negative women with first trimester spontaneous abortions to prevent maternal sensitization to the fetal Rh antigen and subsequent fetal morbidity and mortality.

Methods

We searched MEDLINE (1966-2005), the Cochrane Central Register of Controlled Trials, EMBASE (1990 to 2005), and the reference sections of the articles found. The search is considered updated to December of 2005. Search terms included vaginal bleeding, Rh negative, Rh immune globulin, RhoGAM, isoimmunization, sensitization, first trimester pregnancy, threatened, and spontaneous abortion.

Results

The evidence to support the use of Rh immune globulin for a diagnosis of first trimester spontaneous abortion is minimal. There is a paucity of well-designed research that examines maternal sensitization or hemolytic disease of the newborn as an outcome in patients receiving, versus not receiving, Rh immune globulin in first trimester bleeding. There is significant evidence to demonstrate fetomaternal hemorrhage in first trimester spontaneous abortions; yet, no studies demonstrate subsequent maternal sensitization or development hemolytic disease in the fetus as a result of this hemorrhage.

Conclusion

In summary, there is minimal evidence that administering Rh immune globulin for first trimester vaginal bleeding prevents maternal sensitization or development of hemolytic disease of the newborn. The practice of administering Rh immune globulin to Rh-negative women with a first trimester spontaneous abortion is based on expert opinion and extrapolation from experience with fetomaternal hemorrhage in late pregnancy. Its use for first trimester bleeding is not evidence-based.

Section snippets

Clinical scenario

A 22-year-old G2P1 woman at 9 weeks gestation presents to the ED with lower abdominal cramping and vaginal bleeding for 2 days. Physical examination is unremarkable except for a closed cervical os. Beta human chorionic gonadotropin and transvaginal ultrasound are consistent with a single intrauterine pregnancy at 9 weeks of gestation. The patient's blood type is A negative. Should the ED physician administer Rh immune globulin (RhIG)? Has it been shown to decrease maternal sensitization or

Methods

We searched MEDLINE (1966-2005), the Cochrane Central Register of Controlled Trials, EMBASE (1990 to 2005), and the reference sections of the articles found. The search is considered updated to December of 2005. Search terms included vaginal bleeding, Rh negative, RhIG, RhoGAM, isoimmunization, sensitization, first trimester pregnancy, threatened, and spontaneous abortion.

What is the evidence?

Type of study found	No. of articles
Randomized control trials	1 [1]
Case control	1 [2]
Case reports	1 [3]
Review article	4 [4], [5], [6], [7]
Expert opinion	8 [8], [9], [10], [11], [12], [13], [14], [15]
Fetomaternal hemorrhage/transfusion	7 [16], [17], [18], [19], [20], [21], [22]

A single double-blind randomized control trial was published in 1972 to examine the use of RhIG and subsequent sensitization after a first trimester spontaneous abortion [1]. Although methodologically sound, the study population

Applying the evidence

Clinical evidence does not support the use of RhIG for first trimester threatened abortions in Rh-negative women. There is a paucity of well-designed studies that examine maternal sensitization after a first trimester threatened abortion. There is significant evidence to demonstrate fetomaternal hemorrhage in first trimester spontaneous abortions; yet, no studies demonstrate subsequent maternal sensitization as a result of this hemorrhage. At best, one needs to extrapolate the quantity of

Conclusions

Current studies do not support the use of RhIG for first trimester bleeding in Rh-negative patients, although the risk of its administration is extremely low. Only a single randomized control trial was encountered in examining this question, and it is unlikely that more will be undertaken in the near future. Most experts agree that if the etiology of the bleeding is trauma or if the gestational age is uncertain, then RhIG should be given. Although the tradition of giving RhIG to all Rh-negative

References (22)

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Do Rh-negative women with an early spontaneous abortion need Rh immune prophylaxis?
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A case of Rh isoimmunization: should threatened first-trimester abortion be an indication for Rh immune globulin prophylaxis?
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Vaginal bleeding in the first 20 weeks of pregnancy
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Controversies in Rh prophylaxis. Who needs Rh immune globulin and when should it be given?
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Is Rh immune globulin needed in early first-trimester abortion? A Review
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S.J. Urbaniak
The scientific basis of antenatal prophylaxis
Br J Obstet Gynaecol
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L. Weinberg
Use of anti-D immunoglobulin in the treatment of threatened miscarriage in the accident and emergency department
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Threatened miscarriage: evaluation and management
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Anti-D immunoglobulin in RhD prophylaxis

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Cited by (13)

Prevention of Rhesus-D Alloimmunization in the First Trimester of Pregnancy: Economic Analysis of Three Management Strategies
2024, Transfusion Medicine Reviews
Anti-D alloimmunization in the first trimester of pregnancy has long been the subject of prevention with anti-D immunoglobulins during events at risk of fetomaternal hemorrhage. Although the efficacy of preventing anti-D alloimmunization by an injection of immunoglobulin at 28 weeks of gestation (WG) is obvious, the literature provides little evidence of the effectiveness before 12⁺⁶ WG and several countries have modified their recommendations. In the presumed absence of a difference in alloimmunization risk between early and late prevention, our objective was to evaluate and compare the cost of treatment for 3 alloimmunization prevention strategies in France, the United Kingdom, and the Netherlands. This was a single-center retrospective study. Our target population included all women who received anti-D immunoglobulins (Rhophylac) in the first trimester of pregnancy before 12⁺⁶ WG at Nantes University Hospital in 2018 (N = 356). Within the target population, 2 other populations were constituted based on British (N = 145) and Dutch (N = 142) clinical practice guidelines (CPG). These 3 populations were analyzed for the comparative cost of treatment for prevention from a health system perspective. The average cost of Rhophylac alloimmunization prevention for 1 episode was €117.8 from a health system perspective. The total cost attributed to prevention in 2018 at Nantes University Hospital (N = 356) was €41,931.4 according to this perspective. If the UK CPG or Dutch CPG had been applied to the Nantes target population, a saving of around 60% would have been achieved. At the national level, the cost according to the health system perspective specifically attributable to induced abortion (N estimated = 26,916) could represent a total cost of €3,170,704. This study highlighted the high cost of the French prevention strategy in the first trimester of pregnancy compared with British or Dutch strategies. The modification of our practices would allow substantial financial savings to the French health system but would also avoid the nonrecommended exposure to a blood product at this term, would allow a faster medical management and a relief of the care system.
“Provoked” feto-maternal hemorrhage may represent insensible cell exchange in pregnancies from 6 to 22 weeks gestational age
2019, Contraception
Citation Excerpt :
Moreover, the characterization of early antigenic expression and thus the immunologic significance of fetal red blood cells has also been limited [11–13]. Regardless, it is common for some small volume of fetal cells to enter the maternal circulation during normal pregnancy [14–16]. Given the uncertainty surrounding risk for sensitization across gestational ages and risk events, the American College of Obstetricians and Gynecologists (ACOG) recommends consideration of treatment for all Rh-negative women with vaginal bleeding, first-trimester miscarriage, amniocentesis, CVS, and ectopic pregnancy at any point in gestation [17].
To quantify spontaneous and provoked fetal to maternal cell exchange in the first half of pregnancy. Transfer of fetal red blood cells (FRBCs) into the maternal circulation during the first half of pregnancy is poorly characterized but of clinical relevance for miscarriage management and invasive procedures.
Prospective, descriptive cohort study of women presenting for surgical termination of pregnancy with sonographically confirmed gestational age (GA). Pre-procedural and post-procedural blood samples were collected to characterize both spontaneous (pre) and provoked (post) cell exchange with analysis via flow cytometry to quantify FRBC count.
A total of 100 patients at 6–22 weeks GA contributed 200 matched pre- and post-procedural samples. FRBCs were identified in 69 patients including 4 who exhibited FRBCs pre-procedure only and 9 post-procedure only, for a total of 65 patients having post-procedural FRBCs. Of patients with FRBCs following their procedure, the majority (n=56, 86%) also exhibited evidence of cells before the procedure with just 9 patients (14%) exhibiting FRBCs only after. No dose–response relationship was appreciable between GA and FRBC count.
After experiencing disruption of the placenta with instrumentation, roughly two thirds of patients had detectable FRBCs in maternal circulation following their procedure but—among those that did—the majority also exhibited cell presence prior to the procedure. This leads to further questions regarding the relationship between risk events and alloimmunization potential in previable pregnancies as the rate of spontaneous transplacental cell exchange may be underappreciated and the magnitude of provoked transfer may be overestimated.
The relationship between feto-maternal hemorrhage risk events and alloimmunization potential in previable pregnancies has previously been poorly characterized but these data reveal spontaneous transplacental cell exchange may be underappreciated and the magnitude of provoked transfer may be overestimated.
Complications in Early Pregnancy
2019, Emergency Medicine Clinics of North America
Citation Excerpt :
RhIG should be given in all Rh-negative women undergoing surgical treatment for miscarriage and in any ectopic pregnancy.38 ACOG states that as the risk of allo-immunization is low in early first-trimester spontaneous miscarriage treated nonsurgically, but RhIG treatment should be considered based on expert opinion and extrapolation of third-trimester fetomaternal hemorrhage.39,40 Dosing varies from 50 μg to 120 μg if given before 12 weeks; 300 μg is given if after 12 weeks.
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
2019, Contraception: X
Citation Excerpt :
While Rh alloimmunization may harm subsequent pregnancies, there is a lack of evidence that this occurs in early gestations. Canada and many other countries recommend offering anti-D IgG to all Rh-negative women at the time of a spontaneous or an induced abortion in order to block alloimmunization [1,2]. Although fetal RBCs can express the D-antigen as early as 52 days after the last menstrual period (LMP) [3], we lack convincing evidence for the benefit of using anti-D in the first trimester [4].
The objective of this study was to compare Rh alloimmunization rates in two countries (Canada and the Netherlands) with completely different policies regarding abortion-related use of anti-D immunoglobulin to ultimately determine any benefit in use. In the Netherlands, the policy is to offer anti-D immunoglobulin to Rh-negative women having spontaneous abortions over 10 weeks 0 days gestation and induced abortions over 7 weeks 0 days. In Canada, it is recommended to offer all Rh-negative women having induced or spontaneous abortions anti-D immunoglobulin.
We used public databases to obtain the population data, the number of births, the abortion rates (the percentage of women having induced abortions in one year) and the Rh-negativity rates (percentage of Rh negative women) in Canada and the Netherlands. Both countries do routine prenatal blood screening and we obtained the rates of clinically significant antibodies from public databases.
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. Canada and the Netherlands had small differences in rates of abortion (1.9 per 100 vs 1.2 per 100) and of Rh negativity (13.0% vs 14.5%).
Despite different anti-D Ig treatment policies, we found a similar prevalence of clinically significant perinatal antibodies among women in Canada and the Netherlands.
Our findings suggest that The Dutch policy of not treating Rh-negative women having spontaneous abortions under 10 weeks’ or induced abortions under 7 weeks’ gestation can be safely adopted by other countries.
Emergencies in Early Pregnancy
2012, Emergency Medicine Clinics of North America
Citation Excerpt :
Although the administration of RhIG has been shown to be effective in reducing maternal sensitization and fetal morbidity and mortality peripartum and during the third trimester,28 its use during the first trimester remains controversial. There is little evidence to support the use of first-trimester RhIG; however, it has become standard of care as a result of expert opinion and extrapolation on experience with third-trimester fetomaternal hemorrhage.29,30 The current recommendations by the American College of Obstetricians and Gynecologists state that all unsensitized Rh-negative pregnant women should be given RhIG within 72 hours of abortion.
Office management of early pregnancy loss
2011, American Family Physician
Citation Excerpt :
Although there is no direct evidence to support this practice in very early pregnancy, it remains the standard of care in the United States. The dose of Rho(D) immune globulin is 50 mcg (250 IU) in women with bleeding before 12 completed weeks' gestation.58 Women with heavy bleeding or signs and symptoms of anemia should have their hemoglobin level checked.
The management of early pregnancy loss used to be based largely in the hospital setting, but it has shifted to the outpatient setting, allowing women to remain under the care of their family physician throughout the miscarriage process. Up to 15 percent of recognized pregnancies end in miscarriage, and as many as 80 percent of miscarriages occur in the first trimester, with chromosomal abnormalities as the leading cause. In general, no interventions have been proven to prevent miscarriage; occasionally women can modify their risk factors or receive treatment for relevant medical conditions. Unless products of conception are seen, the diagnosis of miscarriage is made with ultrasonography and, when ultrasonography is not available or is nondiagnostic, with measurement of beta subunit of human chorionic gonadotropin levels. Management options for early pregnancy loss include expectant management, medical management with misoprostol, and uterine aspiration. Expectant management is highly effective for the treatment of incomplete abortion, whereas misoprostol and uterine aspiration are more effective for the management of an embryonic gestation and embryonic demise. Misoprostol in a dose of 800 meg administered vaginally is effective and well-tolerated. Compared with dilation and curettage in the operating room, uterine aspiration is the preferred procedure for early pregnancy loss; aspiration is equally safe, quicker to perform, more cost-effective, and amenable to use in the primary care setting. All management options are equally safe; thus, patient preference should guide treatment choice.

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^☆: Disclosures: The authors received no outside funding, support, or compensation for this project.

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ControversiesDo Rh-negative women with first trimester spontaneous abortions need Rh immune globulin?☆

Abstract

Objective

Methods

Results

Conclusion

Section snippets

Clinical scenario

Methods

What is the evidence?

Applying the evidence

Conclusions

Am J Obstet Gynecol

Am J Obstet Gynecol

Emerg Med Clin North Am

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Transvaginal bleeding during pregnancy associated with Rhesus-D isoimmunization

Salud Pública de Méx

The scientific basis of antenatal prophylaxis

Br J Obstet Gynaecol

Use of anti-D immunoglobulin in the treatment of threatened miscarriage in the accident and emergency department

Emerg Med J

Threatened miscarriage: evaluation and management

BMJ

Anti-D immunoglobulin in RhD prophylaxis

Br J Obstet Gynaecol

Controversies
Do Rh-negative women with first trimester spontaneous abortions need Rh immune globulin?☆