Abstract
Objective
To estimate the rate of requiring more than one 300-mcg Rh D immune globulin dose for fetomaternal hemorrhage (FMH) at the time of second-trimester dilation and evacuation (D + E).
Study design
We performed a retrospective cohort analysis of patients at greater than 20 weeks’ gestation who underwent D + E, had Rh D-negative blood type, and received FMH quantification testing.
Results
Of 25 eligible patients, 24 had negative quantification of FMH; one had positive quantification that did not meet the clinical threshold for additional dosing.
Conclusions
The absolute risk of requiring additional Rh D immune globulin after D+E for pregnancies greater than 20 weeks’ gestation was 0%.
Keywords
1. Introduction
Fetomaternal hemorrhage (FMH) may occur during first- and second-trimester miscarriage and induced abortion and may lead to subsequent alloimmunization among Rh D-negative patients [
[1]
]. Rh D immune globulin is effective at preventing Rh alloimmunization, and United States clinical guidelines recommend a 300-mcg dose for gestations greater than 12 weeks, which provides protection for up to 30 mL fetal Rh-positive whole blood [[2]
,[3]
]. This dose may not be necessary after uterine evacuation procedures in the first trimester [[4]
] and is sufficient for pregnancies up to 20 weeks’ gestation, at which point total fetal blood volume is estimated to be 30 mL [[5]
]. Beyond 20 weeks’ gestation, some recommend quantitative assessment of FMH volume to precisely dose Rh D immune globulin and ensure prevention of Rh alloimmunization [[6]
]. The volume of FMH after uterine evacuation after 20 weeks’ gestation and corresponding Rh D immune globulin dose requirement are not well studied.We conducted a retrospective cohort study of Rh D-negative patients undergoing dilation and evacuation (D + E) between 20 and 24 weeks of gestation to determine the proportion with positive FMH quantification testing above a clinical threshold to require additional Rh D immune globulin.
2. Material and Methods
This was a retrospective cohort study of patients at greater than 20 weeks’ gestation who underwent D + E between 2011 and 2019, had Rh D-negative blood type, and received quantification testing for FMH at the time of their procedure. All D + E procedures performed in the operating room between 2011 and 2019 were reviewed and eligible patients underwent a full chart review. All patients, except for one, underwent one day of osmotic dilation with dilators prior to their procedure. Study data were collected and managed using REDCap electronic data capture tools hosted by the University of Pennsylvania. We recorded demographic characteristics, medical and surgical history, index pregnancy characteristics, procedural details, Rh status, FMH quantification result, and number of doses of Rh D immune globulin administered. The protocol for this study was approved by the University of Pennsylvania Institutional Review Board.
At our institution, patients with Rh D-negative blood type typically receive 300 mcg of Rh D immune globulin after D&E at all gestational ages. In addition, after 20 weeks’ gestation, some surgical providers send a patient blood sample after the procedure in order to quantify FMH. Our blood bank has defined a result of 7.4 mL of estimated fetal cell volume as the threshold for administration of an additional 300-mcg dose of Rh D immune globulin. Our study population spans two sites, one of which assesses FMH using the Kleihauer-Betke (K-B) test and the other of which uses flow cytometry.
The primary outcome was the proportion of patients who have a positive FMH quantification result above the clinical threshold of 7.4 mL. We also assessed the proportion of patients with any positive FMH quantification result. We used descriptive statistics to summarize our findings. An absolute risk of a positive FMH quantification result was calculated. All data analysis was performed in STATA 15.1 (College Station, TX).
3. Results
Of 2233 charts reviewed, 25 patients were eligible for inclusion in the study. The majority of patients were excluded due to being Rh D-positive blood type or less than 20 weeks in gestation Table 1. describes the demographic characteristics of this cohort Table 2. describes pregnancy and procedural characteristics. The median gestational age at the time of procedure was 21 weeks and 2 days. Five procedures were complicated by estimated blood loss greater than 500 mL, 3 of whom required transfusions. One patient had a fever during her clinical course and required antibiotics. Nineteen (76%) patients had their FMH quantification completed by flow cytometry and 6 (24%) had theirs done by K-B test.
Table 1Demographic characteristics of patients undergoing Dilation and Evacuation at the University of Pennsylvania Health System between 2011 and 2019 at greater than 20 weeks’ gestation who had Rh negative blood type and testing for fetomaternal hemorrhage quantification (N = 25)
| N, Mean ± SD, Median (IQR) | |
|---|---|
| Age | 28.3 ±5.1 |
| Race | |
| Black/African American | 14 |
| White | 9 |
| Other | 2 |
| Ethnicity | |
| Hispanic/LatinX | 2 |
| Non-Hispanic | 23 |
| Gravidity | |
| 1 | 4 |
| 2 | 4 |
| 3 | 5 |
| 4+ | 12 |
| Parity | |
| 0 | 4 |
| 1 | 9 |
| 2 | 5 |
| 3+ | 7 |
| BMI | 32.3 (24.8-36.3) |
| Insurance Status | |
| Private | 7 |
| Public | 15 |
| None | 3 |
Table 2Characteristics of index pregnancy and procedural information of patients undergoing Dilation and Evacuation at the University of Pennsylvania Health System between 2011 and 2019 at greater than 20 weeks’ gestation who had Rh negative blood type and testing for fetomaternal hemorrhage quantification(N = 25)
| N (%) or Median (IQR) | |
|---|---|
| Gestational age | 21w2d (20w1d–21w4d) |
| Indication for procedure | |
| Induced abortion | 21 |
| IUFD | 4 |
| Estimated blood loss | 200 (100–300) |
| <500 mL | 20 |
| ≥500 mL | 5 |
| Complications- Yes | 5 |
| Uterotonic use | |
| Yes | 7 |
| Administration of Rh D immune globulin earlier in index pregnancy | |
| Yes | 4 |
Twenty-four (96%) of patients had a negative quantification of FMH and received the standard single dose of Rh D immune globulin. The single patient who had a positive result (2 mL) did not meet our institution's clinical threshold for administration of additional Rh D immune globulin, but still received an additional dose out of caution after discussion between the surgeon and the blood bank. Thus, the absolute risk of requiring a second dose of Rh D immune globulin based on the clinical threshold was 0%. The absolute risk of receiving a second postprocedural dose of Rh D immune globulin was 4%.
Subsequent pregnancy information was available for 10 (40%) of participants. Of these, one patient had evidence of isoimmunization. This patient received a single dose of Rh D immune globulin after D + E during the index pregnancy and had a negative quantification of FMH at the time of her procedure as well as an estimated blood loss of 150 mL with no complications during the case.
4. Discussion
Of 25 Rh D-negative patients undergoing D&E between 20 and 24 weeks’ gestation, none met the FMH quantification threshold that required additional dosing of Rh D immune globulin. Our findings are consistent with previous studies examining FMH after second-trimester induced abortion. Testing for fetomaternal hemorrhage at the time of second trimester abortion is not recommended and the findings of this study support previous clinical guidelines that only routine administration of Rh immune globulin is necessary [
[3]
,[7]
]. A prospective study of 31 patients undergoing second-trimester termination of pregnancy with fetal anomalies documented a 3% rate of FMH ≥30 mL using flow cytometry for determination of FMH [[8]
]. In this sample, all pregnancies were affected by fetal anomaly and the majority underwent induction termination. A larger prospective study of 300 patients undergoing second-trimester D + E for induced abortion demonstrated two patients (1%) with FMH ≥30 mL [[9]
].Our study examined FMH at the time of D + E and included a broader range of indications, both induced abortion and fetal demise, compared to previous studies. However, this report remains limited by a small sample size and incomplete data regarding subsequent pregnancies. In addition, it is likely that the different FMH quantification methods across our sites could result in inconsistent FMH estimates, given that K-B does not distinguish between fetal hemoglobin and maternal F cells, and therefore could lead to a misclassification of the outcome. Flow cytometry is generally considered more precise and is preferred when available [
[2]
]. However, despite increased precision most labs use the same calculation to determine the need for additional Rh immune globulin dosing [[10]
]. FMH quantification estimates and clinical thresholds for intervention may vary across institutions, thus it is not clear if these results can be generalized.The absolute risk of FMH quantification above our institution's clinical threshold for additional Rh D immune globulin after D + E for pregnancies greater than 20 weeks of gestation was 0%. The degree of FMH during D + E between 20 and 24 weeks’ gestation rarely warrants more than 300 mcg of Rh D immune globulin, and additional testing may lead to over-treatment and over-utilization of resources. Larger prospective studies that include a range of pregnancy indications, as well as multiple pregnancies, are necessary prior to re-evaluating guidelines surrounding Rh-immune prophylaxis.
References
- Anti-D administration after spontaneous miscarriage for preventing Rhesus alloimmunisation.Cochrane Database Syst Rev. 2013; Cd009617
- Kleihauer Betke Test. StatPearls Treasure Island (FL).StatPearls Publishing StatPearls Publishing LLC, 2020
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- 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
- Fetomaternal hemorrhage.Obstet Gynecol. 2010; 115: 1039-1051
- 133-Prevention of Rh Alloimmunization.J Obstet Gynaecol Can. 2018; 40: e1-e10
- Clinical Policy Guidelines for Abortion Care.National Abortion Federation, Washington, DC2020
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- Inaccurate doses of Rh immune globulin after Rh-incompatible fetomaternal hemorrhage: survey of laboratory practice.Archives of Pathology & Laboratory Medicine. 2009; 133: 465-469
Article info
Publication history
Published online: February 19, 2022
Accepted:
February 11,
2022
Received in revised form:
February 9,
2022
Received:
December 9,
2021
Footnotes
☆Declaration of Competing Interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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